Scavenger receptor-AI-targeted ultrasmall gold nanoclusters facilitate in vivo MR and ex vivo fluorescence dual-modality visualization of vulnerable atherosclerotic plaques.
Wang Jiahui,Wu Menglin,Chang Jin,Li Liang,Guo Qi,Hao Jianwen,Peng Qizhen,Zhang Baoshuai,Zhang Xuening,Li Xue
Nanomedicine : nanotechnology, biology, and medicine
Owing to the high morbidity and mortality of cardiovascular diseases resulting from atherosclerosis, developing specific noninvasive diagnostic methods to distinguish vulnerable atherosclerotic plaques becomes urgent and mandatory. Herein, scavenger receptors AI (SR-AI), a secreted biomarker associated with foam macrophages, was selected as a target for identifying vulnerable plaques. A dual-modality imaging probe (PP1-Au@GSH@Gd NCs) was constructed by covalently attaching a peptidic SR-AI ligand, PP1 to gadolinium-integrated gold nanoclusters, which exhibited remarkably improved fluorescence signal and longitudinal relaxivity with highly loaded Au and Gd species. In vitro cellular binding studies showed preferential affinity of PP1-Au@GSH@Gd NCs to activated macrophages in SR-AI-dependent manner. In vivo MR/fluorescence images presented robust and prolonged plaque contrast enhancement in established ApoE mice models thanks to favorable targeting efficacy of PP1-Au@GSH@Gd NCs. Collectively, the noninvasive MR/fluorescence molecular imaging strategy with PP1-Au@GSH@Gd NCs holds great promise for precise clinical diagnosis of vulnerable plaques.
10.1016/j.nano.2019.04.003
Surface enhanced Raman spectroscopy-detection of the uptake of mannose-modified nanoparticles by macrophages in vitro: A model for detection of vulnerable atherosclerotic plaques.
Dugandžić Vera,Drikermann Denis,Ryabchykov Oleg,Undisz Andreas,Vilotijević Ivan,Lorkowski Stefan,Bocklitz Thomas W,Matthäus Christian,Weber Karina,Cialla-May Dana,Popp Jürgen
Journal of biophotonics
Atherosclerosis is a process of thickening and stiffening of the arterial walls through the accumulation of lipids and fibrotic material, as a consequence of aging and unhealthy life style. However, not all arterial plaques lead to complications, which can lead to life-threatening events such as stroke and myocardial infarction. Diagnosis of the disease in early stages and identification of unstable atherosclerotic plaques are still challenging. It has been shown that the development of atherosclerotic plaques is an inflammatory process, where the accumulation of macrophages in the arterial walls is immanent in the early as well as late stages of the disease. We present a novel surface enhanced Raman spectroscopy (SERS)-based strategy for the detection of early stage atherosclerosis, based on the uptake of tagged gold nanoparticles by macrophages and subsequent detection by means of SERS. The results presented here provide a basis for future in vivo studies in animal models.The workflow of tracing the SERS-active nanoparticle uptake by macrophages employing confocal Raman imaging.
10.1002/jbio.201800013
Silica-gold nanoparticles for atheroprotective management of plaques: results of the NANOM-FIM trial.
Kharlamov Alexander N,Tyurnina Anastasiya E,Veselova Vera S,Kovtun Olga P,Shur Vladimir Y,Gabinsky Jan L
Nanoscale
BACKGROUND:Atheroregression becomes an attractive target for cardiovascular treatment. Some clinical trials have demonstrated that intensive therapy with rosuvastatin or recombinant ApoA-I Milano can partially reduce the total atheroma volume (TAV) up to 6.38 mm(3) or 14.1 mm(3) respectively. Our previous bench studies of selected nanotechnologies documented TAV reduction up to an unprecedented 79.4 mm(3). METHODS:The completed observational three arms (n = 180) first-in-man trial (the NANOM FIM trial) assessed (NCT01270139) the safety and feasibility of two delivery techniques for nanoparticles (NP), and plasmonic photothermal therapy (PPTT). Patients were assigned to receive either (1) nano-intervention with delivery of silica-gold NP in a bioengineered on-artery patch (n = 60), or (2) nano-intervention with delivery of silica-gold iron-bearing NP with targeted micro-bubbles and stem cells using a magnetic navigation system (n = 60) versus (3) stent implantation (n = 60). The primary outcome was TAV at 12 months. RESULTS:The mean TAV reduction at 12 months in the Nano group was 60.3 mm(3) (SD 39.5; min 41.9 mm(3), max 94.2 mm(3); p < 0.05) up to mean 37.8% (95% CI: 31.1%, 51.7%; p < 0.05) plaque burden. The analysis of the event free survival of the ongoing clinical follow-up shows the significantly lower risk of cardiovascular death in the Nano group when compared with others (91.7% vs. 81.7% and 80% respectively; p < 0.05) with no cases of the target lesion-related complications. CONCLUSIONS:PPTT using silica-gold NP associated with significant regression of coronary atherosclerosis.
10.1039/c5nr01050k
Gold nanoparticles-based SPECT/CT imaging probe targeting for vulnerable atherosclerosis plaques.
Li Xiao,Wang Cong,Tan Hui,Cheng Leilei,Liu Guobing,Yang Yi,Zhao Yanzhao,Zhang Yiqiu,Li Yanli,Zhang Chunfu,Xiu Yan,Cheng Dengfeng,Shi Hongcheng
Biomaterials
In order to realize accurate localization and precise evaluation of vulnerability of atherosclerotic plaques via dual-modal imaging, gold nanoparticles (GNPs) were firstly caped with a thin amino-PEGs cover and then conjugated with the targeting molecular Annexin V and radionuclide Tc-99m simultaneously to form SPECT/CT imaging probe targeting apoptotic macrophages. The as-synthesized (99m)Tc-GNPs-Annexin V was with uniform size (30.2 ± 2.9 nm) and high labeling rate (98.9 ± 0.5%) and stability. Targeting ability of Annexin V for apoptotic macrophages was kept and enhanced. For macrophages with 30% apoptosis, cellular uptakes of 3.52 ± 0.35% for (99m)Tc-GNPs-Annexin V, 2.41 ± 0.53% for (99m)Tc-GNPs and 1.68 ± 0.36% for (99m)Tc-Annexin V were achieved after 2 h incubation. ApoE knock out mice with high fat diet-induced atherosclerosis were scanned via (99m)Tc-GNPs-Annexin V SPECT/CT. With the introduction of targeting molecules, imaging probe was more efficient in accumulating in apoptotic macrophages. In practical evaluation, CT helps to restrict the lesions depiction more accurately, meanwhile, SPECT imaging intensity correlated with pathological changes tightly. In conclusion, Annexin V-modified hybrid gold nanoparticles were successfully synthesized, and this imaging system helped to better localize and diagnose those vulnerable AS plaques via specific targeting the apoptotic macrophages.
10.1016/j.biomaterials.2016.08.048
Thrombin-activatable fluorescent peptide incorporated gold nanoparticles for dual optical/computed tomography thrombus imaging.
Kwon Sung-Pil,Jeon Sangmin,Lee Sung-Hoon,Yoon Hong Yeol,Ryu Ju Hee,Choi Dayil,Kim Jeong-Yeon,Kim Jiwon,Park Jae Hyung,Kim Dong-Eog,Kwon Ick Chan,Kim Kwangmeyung,Ahn Cheol-Hee
Biomaterials
Thrombosis is an important pathophysiologic phenomenon in various cardiovascular diseases, which can lead to oxygen deprivation and infarction of tissues by generation of a thrombus. Thus, direct thrombus imaging can provide beneficial in diagnosis and therapy of thrombosis. Herein, we developed thrombin-activatable fluorescent peptide (TAP) incorporated silica-coated gold nanoparticles (TAP-SiO@AuNPs) for direct imaging of thrombus by dual near-infrared fluorescence (NIRF) and micro-computed tomography (micro-CT) imaging, wherein TAP molecules were used as targeted thrombin-activatable peptide probes for thrombin-specific NIRF imaging. The freshly prepared TAP-SiO@AuNPs had an average diameter of 39.8 ± 2.55 nm and they showed the quenched NIRF signal in aqueous condition, due to the excellent quenching effect of TAP molecules on the silica-gold nanoparticle surface. However, 30.31-fold higher NIRF intensity was rapidly recovered in the presence of thrombin in vitro, due to the thrombin-specific cleavage of quenched TAP molecules on the gold particle surface. Furthermore, TAP-SiO@AuNPs were successfully accumulated in thrombus by their particle size-dependent capturing property, and they presented a potential X-ray absorption property in a dose-dependent manner. Finally, thrombotic lesion was clearly distinguished from peripheral tissues by dual NIRF/micro-CT imaging after intravenous injection of TAP-SiO@AuNPs in the in situ thrombotic mouse model, simultaneously. This study showed that thrombin-activatable fluorescent peptide incorporated silica-coated gold nanoparticles can be potentially used as a dual imaging probe for direct thrombus imaging and therapy in clinical applications.
10.1016/j.biomaterials.2017.10.017
Personalized Nanotherapy by Specifically Targeting Cell Organelles To Improve Vascular Hypertension.
Pala Rajasekharreddy,Mohieldin Ashraf M,Shamloo Kiumars,Sherpa Rinzhin T,Kathem Sarmed H,Zhou Jing,Luan Zhongyue,Zheng Jian-Guo,Ahsan Amir,Nauli Surya M
Nano letters
Ciliopathies caused by abnormal function of primary cilia include expanding spectrum of kidney, liver, and cardiovascular disorders. There is currently no treatment available for patients with cilia dysfunction. Therefore, we generated and compared two different (metal and polymer) cilia-targeted nanoparticle drug delivery systems (CTNDDS), CT-DAu-NPs and CT-PLGA-NPs, for the first time. These CTNDDS loaded with fenoldopam were further compared to fenoldopam-alone. Live-imaging of single-cell-single-cilium analysis confirmed that CTNDDS specifically targeted to primary cilia. While CTNDDS did not show any advantages over fenoldopam-alone in cultured cells in vitro, CTNDDS delivered fenoldopam more superior than fenoldopam-alone by eliminating the side effect of reflex tachycardia in murine models. Although slow infusion was required for fenoldopam-alone in mice, bolus injection was possible for CTNDDS. Though there were no significant therapeutic differences between CT-DAu-NPs and CT-PLGA-NPs, CT-PLGA-NPs tended to correct ciliopathy parameters closer to normal physiological levels, indicating CT-PLGA-NPs were better cargos than CT-DAu-NPs. Both CTNDDS showed no systemic adverse effect. In summary, our studies provided scientific evidence that existing pharmacological agent could be personalized with advanced nanomaterials to treat ciliopathy by targeting cilia without the need of generating new drugs.
10.1021/acs.nanolett.8b04138
Gold Nanorod-Based Engineered Cardiac Patch for Suture-Free Engraftment by Near IR.
Malki Maayan,Fleischer Sharon,Shapira Assaf,Dvir Tal
Nano letters
Although cardiac patches hold a promise for repairing the infarcted heart, their integration with the myocardium by sutures may cause further damage to the diseased organ. To address this issue, we developed facile and safe, suture-free technology for the attachment of engineered tissues to organs. Here, nanocomposite scaffolds comprised of albumin electrospun fibers and gold nanorods (AuNRs) were developed. Cardiac cells were seeded within the scaffolds and assembled into a functioning patch. The engineered tissue was then positioned on the myocardium and irradiated with a near IR laser (808 nm). The AuNRs were able to absorb the light and convert it to thermal energy, which locally changed the molecular structure of the fibrous scaffold, and strongly, but safely, attached it to the wall of the heart. Such hybrid biomaterials can be used in the future to integrate any engineered tissue with any defected organs, while minimizing the risk of additional injury for the patient, caused by the conventional stitching methods.
10.1021/acs.nanolett.7b04924
Nanoengineered Electroconductive Collagen-Based Cardiac Patch for Infarcted Myocardium Repair.
Hosoyama Katsuhiro,Ahumada Manuel,McTiernan Christopher D,Davis Darryl R,Variola Fabio,Ruel Marc,Liang Wenbin,Suuronen Erik J,Alarcon Emilio I
ACS applied materials & interfaces
We have prepared and tested in vivo a novel nanoengineered hybrid electroconductive cardiac patch for treating the infarcted myocardium. Of the prepared and tested patches, only those containing spherical nanogold were able to increase connexin-43 expression in neonatal rat cardiomyocytes cultured under electrical stimulation. In vivo data indicated that only nano-gold-containing patches were able to recover cardiac function. Histological analysis also revealed that connexin-43 levels and blood vessel density were increased, while the scar size was reduced for animals that received the nanogold patch. Thus, our study indicates that the incorporation of electroconductive properties into a collagen-based cardiac patch can improve its therapeutic potential for treating myocardial infarction.
10.1021/acsami.8b18844
Engineered bioactive nanoparticles incorporated biofunctionalized ECM/silk proteins based cardiac patches combined with MSCs for the repair of myocardial infarction: In vitro and in vivo evaluations.
Dong Yongda,Hong Meiman,Dai Ruozhu,Wu Haiyun,Zhu Ping
The Science of the total environment
The development of cardiac patches by the combination of bioactive nano- and bio-materials with mesenchymal stem cells signifies an auspicious approach for the treatment of cardiac repair in myocardial infarction. In the present investigation, we study about the cardiac function of morphology improved gold nanoparticles combined with extracellular matrix/silk proteins for the cell proliferation and expansion of cardiomyocytes. The physico-chemical and morphological characteristics demonstrated that spherical and homogeneous Au particles are distributed on the matrix porous surface for providing favorable conductivity and biological influences in cardiac repair. The in vitro cell studies of prepared patches have established enhanced cell compatibility and retention of cardiomyocytes survival. The in vivo determinations imply that Au-ESF group decreases infarct size to 65% from 89% in control group. These developed cardiac patches can be highly suitable in the cardiac regeneration and offer new platform in cardiac tissue engineering.
10.1016/j.scitotenv.2019.135976
Diagnostics on acute myocardial infarction: Cardiac troponin biomarkers.
Fathil M F M,Md Arshad M K,Gopinath Subash C B,Hashim U,Adzhri R,Ayub R M,Ruslinda A R,Nuzaihan M N M,Azman A H,Zaki M,Tang Thean-Hock
Biosensors & bioelectronics
Acute myocardial infarction or myocardial infarction (MI) is a major health problem, due to diminished flow of blood to the heart, leads to higher rates of mortality and morbidity. Data from World Health Organization (WHO) accounted 30% of global death annually and expected more than 23 million die annually by 2030. This fatal effects trigger the need of appropriate biomarkers for early diagnosis, thus countermeasure can be taken. At the moment, the most specific markers for cardiac injury are cardiac troponin I (cTnI) and cardiac troponin T (cTnT) which have been considered as 'gold standard'. Due to higher specificity, determination of the level of cardiac troponins became a predominant indicator for MI. Several ways of diagnostics have been formulated, which include enzyme-linked immunosorbent assay, chemiluminescent, fluoro-immunoassays, electrical detections, surface plasmon resonance, and colorimetric protein assay. This review represents and elucidates the strategies, methods and detection levels involved in these diagnostics on cardiac superior biomarkers. The advancement, sensitivity, and limitations of each method are also discussed. In addition, it concludes with a discussion on the point-of care (POC) assay for a fast, accurate and ability of handling small sample measurement of cardiac biomarker.
10.1016/j.bios.2015.03.037
Diagnosis and prognosis of myocardial infarction on a plasmonic chip.
Xu Wei,Wang Lin,Zhang Ru,Sun Xuming,Huang Lin,Su Haiyang,Wei Xunbin,Chen Chia-Chun,Lou Jiatao,Dai Hongjie,Qian Kun
Nature communications
Cardiovascular diseases lead to 31.5% of deaths globally, and particularly myocardial infarction (MI) results in 7.4 million deaths per year. Diagnosis of MI and monitoring for prognostic use are critical for clinical management and biomedical research, which require advanced tools with accuracy and speed. Herein, we developed a plasmonic gold nano-island (pGold) chip assay for diagnosis and monitoring of MI. On-chip microarray analysis of serum biomarkers (e.g., cardiac troponin I) afforded up to 130-fold enhancement of near-infrared fluorescence for ultra-sensitive and quantitative detection within controlled periods, using 10 μL of serum only. The pGold chip assay achieved MI diagnostic sensitivity of 100% and specificity of 95.54%, superior to the standard chemiluminescence immunoassay in cardiovascular clinics. Further, we monitored biomarker concentrations regarding percutaneous coronary intervention for prognostic purpose. Our work demonstrated a designed approach using plasmonic materials for enhanced diagnosis and monitoring for prognostic use towards point-of-care testing.
10.1038/s41467-020-15487-3
Nanomaterial-based biosensors and immunosensors for quantitative determination of cardiac troponins.
Nezami Alireza,Dehghani Sadegh,Nosrati Rahim,Eskandari Negar,Taghdisi Seyed Mohammad,Karimi Gholamreza
Journal of pharmaceutical and biomedical analysis
Cardiovascular diseases (CVDs) are the most frequent mortality cause in many countries. The acute myocardial infraction (AMI) is one of the most common types of CVDs. Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) as predominant cardiac infarction biomarkers considered as "gold standard" for diagnosis of acute myocardial infraction (AMI). The restrictions of traditional methods have encouraged the development of highly sensitive and specific methods for cTnI and cTnT detection. The rapid, early, reliable, and cost-effective diagnosis of CVDs not only helps with patient survival, but also save cost and time to prosperous prognosis. In recent years, the concept of biosensors has opened new horizons in high precision detection. Once combined with nanomaterials, nano-scale biosensors provide powerful analytical platforms for diagnosing of cTnI and cTnT. In this article, after a brief overview of the cardiac troponins, a classification and description of the research progresses of biosensors and immunosensors for the detection and quantitative determination of cardiac troponins based on optical and electrochemical platforms are presented.
10.1016/j.jpba.2018.07.031
Nanoengineering the heart: conductive scaffolds enhance connexin 43 expression.
You Jin-Oh,Rafat Marjan,Ye George J C,Auguste Debra T
Nano letters
Scaffolds that couple electrical and elastic properties may be valuable for cardiac cell function. However, existing conductive materials do not mimic physiological properties. We prepared and characterized a tunable, hybrid hydrogel scaffold based on Au nanoparticles homogeneously synthesized throughout a polymer templated gel. Conductive gels had Young's moduli more similar to myocardium relative to polyaniline and polypyrrole, by 1-4 orders of magnitude. Neonatal rat cardiomyocytes exhibited increased expression of connexin 43 on hybrid scaffolds relative to HEMA with or without electrical stimulation.
10.1021/nl201514a
An Aptamer-Based Near-Infrared Fluorescence Nanoprobe for Detecting and Imaging of Phospholamban Micropeptide in Cardiomyocytes.
Zhan Renhui,Li Xiaofeng,Guo Wenfei,Liu Xiaojun,Liu Zhixian,Xu Kehua,Tang Bo
ACS sensors
A growing body of evidence indicates that micropeptides encoded by long noncoding RNAs (lncRNAs) act independently or as regulators of larger proteins in fundamental biological processes, especially in the maintenance of cellular homeostasis. However, due to their small size and low intracellular expression, visual monitoring of micropeptides in living cells is still a challenge. In this work, we have designed and synthesized an aptamer-based near-infrared fluorescence nanoprobe for fluorescence imaging of phospholamban (PLN), which is an intracellular micropeptide that affects calcium homeostasis, and is closely associated with human heart failure in the clinic. The nanoprobe could respond specifically to PLN with excellent selectivity, high sensitivity, good nuclease stability, and biocompatibility, and it was successfully applied for imaging of changes in PLN levels in cardiomyocytes and in frozen sections of heart tissues. Further combined with clinical myocardial biopsy, we believe that the developed nanoprobe should be of great significance in later molecular pathology study of heart failure, which may help with diagnosis of early heart failure in the future. More importantly, for the first time nanoprobes were applied to visually monitor the changes of micropeptides in living cells and in frozen tissue sections, and the design concept of the aptamer-based nanoprobe can be extended to fluorescence detection of other micropeptides.
10.1021/acssensors.9b00026
Accumulation of gold nano-rods in the failing heart of transgenic mice with the cardiac-specific expression of TNF-α.
Higuchi Yoshihiro,Niidome Takuro,Miyamoto Yuji,Komohara Yoshihiro,Tokunou Tomotake,Kubota Toru,Horiuchi Takahiko
Heart and vessels
Gold nano-rods, rod-shaped gold nanoparticles, act as contrast agents for in vivo bioimaging, drug delivery vehicles and thermal converters for photothermal therapy. Pro-inflammatory cytokines play critical roles in the development of heart failure. We examined the delivery of GNRs into the failing heart of a transgenic (TG) mouse model of inflammatory cardiomyopathy with the cardiac-specific overexpression of TNF-α. We modified GNRs with polyethylene glycol (PEG) to avoid cytotoxicity and reduce the rapid clearance of nanoparticles from blood. PEG-modified GNRs (4.5 mM as gold atoms, 200 μL) were administered intravenously to TG (n = 7) and wild-type (WT) mice (n = 5). These were killed 24 h later, and the heart, lung, liver, kidney and spleen were excised. A quantitative analysis of gold was performed using inductively coupled plasma mass or optical emission spectrometry. The amount of gold (ng) in the TG heart (3.24 ± 1.56 ng/mg heart weight) was significantly greater than that in the WT heart (1.01 ± 0.19; p < 0.05). No significant differences were observed among the other organs of TG and WT mice. The amount of gold in the TG heart was significantly and positively correlated with the ratio of the ventricular weight to body weight, which is known to be an index of ventricular hypertrophy. In conclusion, PEG-modified GNRs accumulated in the inflammatory TG heart in proportion with the severity of ventricular hypertrophy.
10.1007/s00380-018-1241-2
Gold nanoparticles in cardiovascular imaging.
Varna Mariana,Xuan Hoa V,Fort Emmanuel
Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
Although originally applied in the field of oncology, recent results have illustrated the considerable potential of gold nanoparticles (GNPs) in the imaging of cardiovascular diseases (CVDs). CVDs represent the leading cause of mortality and disability in the world. The principal cause underpinning CVDs is atherosclerosis, which develops into mid and large blood vessels, often leading to severe complications. Thanks to their unique physicochemical properties, GNPs have drawn much attention from the research community in cardiovascular imaging. Thus, the optical properties of GNPs have led to their utilization as contrast agents for optical or X-ray imaging modalities allowing the detection of atherosclerotic plaques, intravascular thrombus, or fibrotic tissue. In this study, we detail the most promising preclinical scientific progresses based on the use of GNPs for imaging in cardiovascular field and their improvements for a potential clinical application. WIREs Nanomed Nanobiotechnol 2018, 10:e1470. doi: 10.1002/wnan.1470 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease.
10.1002/wnan.1470
Conjugating Existing Clinical Drugs With Gold Nanoparticles for Better Treatment of Heart Diseases.
Zhang Jingwen,Ma Aiqun,Shang Lijun
Frontiers in physiology
Developing new methods to treat heart diseases is always a focus for basic research and clinical applications. Existing drugs have strong side-effects and also require lifetime administration for patients. Recent attempts of using nanoparticles (NPs) in treating atherosclerosis in animals and some heart diseases such as heart failure and endocarditis have provided hopes for better drug delivery and reducing of drug side-effects. In this mini-review, we summarize the present applications of using gold nanoparticles (GNPs) as a new drug delivery system in diseased hearts and of the assessment of toxicity in using GNPs. We suggest that conjugating existing clinical drugs with GNPs is a favorable choice to provide "new and double-enhanced" potentiality to those existing drugs in treating heart diseases. Other applications of using NPs in the treatment of heart diseases including using drugs in nano-form and coating drugs with a surface of relevant NP are also discussed.
10.3389/fphys.2018.00642
Longitudinal and quantitative assessment platform for concurrent analysis of anti-tumor efficacy and cardiotoxicity of nano-formulated medication in vivo.
Tu Wei-Ming,Huang Xin-Chun,Chen Yen-Ling,Luo Yun-Ling,Liau Ian,Hsu Hsin-Yun
Analytica chimica acta
Increasing nanomedicinal approaches have been developed to effectively inhibit tumor growth; however, critical questions such as whether a nanomedicinal approach can mitigate latent side effects are barely addressed. To this end, we established a zebrafish xenograft tumor model, combining pseudodynamic three-dimensional cardiac imaging and image analysis to enable simultaneous and quantitative determination of the change of tumor volume and cardiac function of zebrafish upon specific nanoformulation treatment. Doxorubicin (DOX), a well-known chemotherapeutic agent with cardiotoxicity, and a recently developed DOX-loaded nanocomposite were employed as two model drugs to demonstrate the effectiveness to utilize the proposed evaluation platform for rapid validation. The nanoformulation significantly mitigated DOX-associated cardiotoxicity, while retaining the efficacy of DOX in inhibiting tumor growth compared to administration of carrier-free DOX at the same dose. We anticipate that this platform possesses the potential as an efficient assessment system for nanoformulated cancer therapeutics with suspected toxicity and side effects to vital organs such as the heart.
10.1016/j.aca.2019.10.019
Simultaneous colorimetric determination of acute myocardial infarction biomarkers by integrating self-assembled 3D gold nanovesicles into a multiple immunosorbent assay.
Pu Qinli,Yang Xuanhua,Guo Yongcan,Dai Tao,Yang Tingyan,Ou Xinying,Li Junlong,Sheng Shangchun,Xie Guoming
Mikrochimica acta
An improved enzyme-free immunosorbent assay is described for the simultaneous detection of the myocardial infarction biomarkers N-terminal pro B type natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), and cardiac muscle troponin T (cTnT). The assay integrates 3D gold nanovesicles (GNVs) and three allochroic agents (phenolphthalein, methyl red, bromothymol blue). The pH regulated allochroic agents were enwrapped in GNVs to acts as ultrasensitive nanoprobes. Loading can be controlled by adjusting the temperature to efficiently load and release the allochroic agents. This bare-eye multicolor assay has limits of detection of 70 pg·mL for NT-proBNP, 910 pg·mL for CK-MB, and 7.8 pg·mL for cTnT. Other features include (a) a linear range that extends over a wide range and sometimes is better than conventional HRP-based immunoassays, and (b) a precision that is comparable to immunofluorescence assays as used in the clinical laboratory. Graphical abstract Schematic presentation of an improved enzyme-free immunosorbent assay (EFISA). It integrates 3D gold nano-vesicles (GNVs) and allochroic agents for the simultaneous detection of acute myocardial infarction (AMI) biomarkers (N-terminal prohormone of brain natriuretic peptide (NT-proBNP), kinase-muscle/brain test (CK-MB), and cardiac muscle troponin (cTnT)).
10.1007/s00604-019-3242-y
In vivo evaluation of enhanced drug carrier efficiency and cardiac anti-hypertrophy therapeutic potential of nano-curcumin encapsulated photo-plasmonic nanoparticles combined polymerized nano-vesicles: A novel strategy.
Liu Yuxiu,Liu Qing,Liu Yingen,Ju Fuxia,Ma Qinghua,He Qin
Journal of photochemistry and photobiology. B, Biology
Curcumin, a naturally derived polyphenolic compound has potent activities against cardiac disease like reducing hypertrophy, increasing antioxidant activity, maintaining hormone levels and blood pressure etc. Polymeric curcumin nanoparticles is a solemn concern nowadays in accordance to improve the beneficial properties of curcumin by diminishing its disadvantages like hydrophobic nature thereby results in maximum delivery of drug curcumin at the target. This study demonstrated the application of curcumin capped gold loaded poly (lactic-co-glycolic acid) nanoparticles (CAu-PLGA Nps) for the inhibition of cardiac hypertrophy by preserving myocardial functions of Wister rat model. Rat models were arbitrarily divided into five groups and observation period was 10 weeks; 1. Control 2. Enalopril (EP), an hypertropic agent induced group 3. EP and Curcumin (C) 4. EP and Curcumin capped gold (CAu) Nps and 5. EP and CAu-PLGA Nps injected group. CAu-PLGA Nps was first synthesized from double emulsion-solvent evaporation method and were characterized by its adoptable techniques such as FT-IR, XRD, SEM and TEM analysis. These analyses demonstrate the encapsulation of curcumin capped gold nanoparticles into PLGA there confirms the successful synthesis of CAu-PLGA Nps. Animals studies illustrates that the CAu-PLGA Nps has significantly produced cardiac anti-hypertrophy and drug delivery when compared to the other groups. CAu-PLGA Nps exhibit increased survival rate, improved cardiac functions like cardiac systolic and diastolic function, maintaining heart weight and left ventricle pressure at the controlled level. Beneficiary activities of CAu-PLGA Nps were associated with its cardiovascular functions like anti-inflammatory, antioxidant, controls cardiomycete growth, increased drug delivery, prevents accumulation of cholesterol and prevents myocardial infarction.
10.1016/j.jphotobiol.2019.111619
Polymer decorated gold nanoparticles in nanomedicine conjugates.
Capek Ignác
Advances in colloid and interface science
Noble metal, especially gold nanoparticles and their conjugates with biopolymers have immense potential for disease diagnosis and therapy on account of their surface plasmon resonance (SPR) enhanced light scattering and absorption. Conjugation of noble metal nanoparticles to ligands specifically targeted to biomarkers on diseased cells allows molecular-specific imaging and detection of disease. The development of smart gold nanoparticles (AuNPs) that can deliver therapeutics at a sustained rate directly to cancer cells may provide better efficacy and lower toxicity for treating cancer tumors. We highlight some of the promising classes of targeting systems that are under development for the delivery of gold nanoparticles. Nanoparticles designed for biomedical applications are often coated with polymers containing reactive functional groups to conjugate targeting ligands, cell receptors or drugs. Using targeted nanoparticles to deliver chemotherapeutic agents in cancer therapy offers many advantages to improve drug/gene delivery and to overcome many problems associated with conventional radiotherapy and chemotherapy. The targeted nanoparticles were found to be effective in killing cancer cells which were studied using various anticancer assays. Cell morphological analysis shows the changes occurred in cancer cells during the treatment with AuNPs. The results determine the influence of particle size and concentration of AuNPs on their absorption, accumulation, and cytotoxicity in model normal and cancer cells. As the mean particle diameter of the AuNPs decreased, their rate of absorption by the intestinal epithelium cells increased. These results provide important insights into the relationship between the dimensions of AuNPs and their gastrointestinal uptake and potential cytotoxicity. Furthermore gold nanoparticles efficiently convert the absorbed light into localized heat, which can be exploited for the selective laser photothermal therapy of cancer. We also review the emerging technologies for the fabrication of targeted gold colloids as imagining agents.
10.1016/j.cis.2017.01.007
Cyanobacteria as Nanogold Factories II: Chemical Reactivity and anti-Myocardial Infraction Properties of Customized Gold Nanoparticles Biosynthesized by sp.
Younis Nancy S,Bakir Esam M,Mohamed Maged E,El Semary Nermin A
Marine drugs
sp., a coccoid, unicellular, nitrogen-fixing and hydrogen-producing cyanobacterium, has been used in this study to biosynthesize customized gold nanoparticles under certain chemical conditions. The produced gold nanoparticles had a characteristic absorption band at 525-535 nm. Two types of gold nanoparticle, the purple and blue, were formed according to the chemical environment in which the cyanobacterium was grown. Dynamic light scattering was implemented to estimate the size of the purple and blue nanoparticles, which ranged from 80 ± 30 nm and 129 ± 40 nm in diameter, respectively. The highest scattering of laser light was recorded for the blue gold nanoparticles, which was possibly due to their larger size and higher concentration. The appearance of anodic and cathodic peaks in cyclic voltammetric scans of the blue gold nanoparticles reflected the oxidation into gold oxide, followed by the subsequent reduction into the nano metal state. The two produced forms of gold nanoparticles were used to treat isoproterenol-induced myocardial infarction in experimental rats. Both forms of nanoparticles ameliorated myocardial infarction injury, with a slight difference in their curative activity with the purple being more effective. Mechanisms that might explain the curative effect of these nanoparticles on the myocardial infarction were proposed. The morphological, physiological, and biochemical attributes of the sp. cyanobacterium were fundamental for the successful production of "tailored" nanoparticles, and complemented the chemical conditions for the differential biosynthesis process. The present research represents a novel approach to manipulate cyanobacterial cells towards the production of different-sized gold nanoparticles whose curative impacts vary accordingly. This is the first report on that type of manipulated gold nanoparticles biosynthesis which will hopefully open doors for further investigations and biotechnological applications.
10.3390/md17070402
Autoantibody profiling on a plasmonic nano-gold chip for the early detection of hypertensive heart disease.
Li Xiaoyang,Kuznetsova Tatiana,Cauwenberghs Nicholas,Wheeler Matthew,Maecker Holden,Wu Joseph C,Haddad Francois,Dai Hongjie
Proceedings of the National Academy of Sciences of the United States of America
The role of autoimmunity in cardiovascular (CV) diseases has been increasingly recognized. Autoimmunity is most commonly examined by the levels of circulating autoantibodies in clinical practices. Measurement of autoantibodies remains, however, challenging because of the deficiency of reproducible, sensitive, and standardized assays. The lack of multiplexed assays also limits the potential to identify a CV-specific autoantibody profile. To overcome these challenges, we developed a nanotechnology-based plasmonic gold chip for autoantibody profiling. This approach allowed simultaneous detection of 10 CV autoantibodies targeting the structural myocardial proteins, the neurohormonal regulatory proteins, the vascular proteins, and the proteins associated with apoptosis and coagulation. Autoantibodies were measured in four groups of participants across the continuum of hypertensive heart diseases. We observed higher levels of all 10 CV autoantibodies in hypertensive subjects ( = 77) compared with healthy participants ( = 30), and the autoantibodies investigated were related to each other, forming a highly linked network. In addition, we established that autoantibodies to troponin I, annexin-A5, and beta 1-adrenegic receptor best discriminated hypertensive subjects with adverse left ventricular (LV) remodeling or dysfunction ( = 49) from hypertensive subjects with normal LV structure and function ( = 28). By further linking these three significant CV autoantibodies to the innate and growth factors, we revealed a positive but weak association between autoantibodies to troponin I and proinflammatory cytokine IL-18. Overall, we demonstrated that this platform can be used to evaluate autoantibody profiles in hypertensive subjects at risk for heart failure.
10.1073/pnas.1621457114
The systematic evaluation of size-dependent toxicity and multi-time biodistribution of gold nanoparticles.
Li Xiaomin,Hu Zhenpeng,Ma Jinlong,Wang Xinyu,Zhang Yapei,Wang Wei,Yuan Zhi
Colloids and surfaces. B, Biointerfaces
As a promising nanomaterial, gold nanoparticles (Au NPs) have been widely applied in diagnosis, drug and gene delivery, and photothermal therapy. However, the toxicity and biodistribution profile of differently sized Au NPs still remains controversial and incomplete, thus hindering their further applications. Herein, a systematic evaluation of size effect on toxicity and multi-time (from 4 h to 90 days) biodistribution of Au NPs ranging from 6.2 nm to 61.2 nm was conducted. The in vitro toxicity by MTT assays manifested that toxicity could be distinctly observed and increased with size decreasing when the dose of Au NPs reached up to a certain amount (1 mM). Subsequently, the corresponding toxicity mechanism was further studied via reactive oxygen species assay kit and the results indicated that Au NPs with various sizes would induce different oxidative stress which was accountable for the ultimate toxicity. Furthermore, the result of the biodistribution showed that Au NPs with larger sizes (42.5 and 61.2 nm) accumulated mainly in liver and spleen while little or none were found in heart, kidney and lung. Dissimilarly, smaller ones (6.2 and 24.3 nm) were distributed not only in liver and spleen but also in other organs. Additionally, most of the Au NPs were excreted out in less than 30 days, whereas there were still bits of remains in liver and spleen up to 90 days, especially for the 42.5 and 61.2 nm Au NPs. These findings are meaningful for the design of the Au NPs in the biomedical fields.
10.1016/j.colsurfb.2018.04.005
Polyethylene-glycol-coated gold nanoparticles improve cardiac function after myocardial infarction in mice.
Tian Aiju,Yang Chengzhi,Zhu Baoling,Wang Wenjing,Liu Kai,Jiang Yunqi,Qiao Yuhui,Fu Haian,Li Zijian
Canadian journal of physiology and pharmacology
Gold nanoparticles (AuNPs) are widely used for drug delivery because of their unique biological properties, such as their safety and ability to prolong drug action. Some studies have demonstrated that AuNPs accumulate in the heart, especially during pathological processes. Therefore, it is very important to understand the effect of AuNPs on the heart. Myocardial infarction (MI) is a major cause of morbidity and mortality; however, the effect of AuNPs on MI remains unclear. In the present study, we carried out a comprehensive evaluation of AuNPs on acute MI. The results showed that AuNPs accumulated in infarcted hearts, decreased infarction size, improved systolic function, and inhibited cardiac fibrosis and TNF-α accumulation. Our work indicated that AuNPs have cardioprotective effects and can be used in drug delivery systems for the treatment of cardiac diseases.
10.1139/cjpp-2018-0227
A Systematic comparison of in vitro cell uptake and in vivo biodistribution for three classes of gold nanoparticles with saturated PEG coatings.
Zhang Yijia,Liu Alice T,Cornejo Yvonne R,Van Haute Desiree,Berlin Jacob M
PloS one
A great deal of attention has been focused on nanoparticles for cancer therapy, with the promise of tumor-selective delivery. However, despite intense work in the field over many years, the biggest obstacle to this vision remains extremely low delivery efficiency of nanoparticles into tumors. Due to the cost, time, and impact on the animals for in vivo studies, the nanoparticle field predominantly uses cellular uptake assays as a proxy to predict in vivo outcomes. Extensive research has focused on decreasing macrophage uptake in vitro as a proxy to delay nanoparticle accumulation in the mononuclear phagocytic system (MPS), mainly the liver and spleen, and thereby increase tumor accumulation. We have recently reported novel synthetic methods employing small molecule crosslinkers for the controlled assembly of small nanoparticles into larger aggregates and found that these nanoaggregates had remarkably high surface coverage and low cell uptake, even in macrophages. We further found that this extremely low cellular uptake could be recapitulated on solid gold nanoparticles by densely coating their surface with small molecules. Here we report our studies on the biodistribution and clearance of these materials in comparison to more conventional PEGylated gold nanoparticles. It was expected that the remarkably low macrophage uptake in vitro would translate to extended blood circulation time in vivo, but instead we found no correlation between either surface coverage or in vitro macrophage cell uptake and in vivo blood circulation. Gold nanoaggregates accumulate more rapidly and to a higher level in the liver compared to control gold nanoparticles. The lack of correlation between in vitro macrophage uptake and in vivo blood circulation suggests that the field must find other in vitro assays to use as a primary proxy for in vivo outcomes or use direct in vivo experimentation as a primary assay.
10.1371/journal.pone.0234916
Co-exposure subacute toxicity of silica nanoparticles and lead acetate on cardiovascular system.
Feng Lin,Yang Xiaozhe,Shi Yanfeng,Liang Shuang,Zhao Tong,Duan Junchao,Sun Zhiwei
International journal of nanomedicine
BACKGROUND:The harmful effects following the release of nanomaterials into environment are of great concern today. PURPOSE:In this study, subacute effect due to co-exposure to low-dose silica nanoparticles (SiNPs) and lead acetate (Pb) on cardiovascular system was detected in Sprague Dawley male rats. MATERIALS AND METHODS:Histopathological and ultrastructural changes of heart, aortic arch and abdominal aorta were detected. Blood routine and blood biochemistry examinations were used to show the changes of blood components. The fibrinolytic and plasmin factors, inflammation-related factors and myocardial-related enzyme in serum were analysised by ELISA and Western blot assay. RESULTS:Histopathological and ultrastructural examination of heart, aortic arch, and abdominal aorta showed that serious damage occurred in co-exposure group (n=6/group). Blood routine examination showed that leukocytosis and thrombocytopenia increased markedly, while changes in the erythrocyte count were not obvious in the co-exposure group. The expression of alanine transaminase (ALT) decreased obviously in co-exposure group, while no significant changes were noted in the expression of aspartate aminotransferase (AST), cholesterol (CHO), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) in the co-exposure group on blood biochemistry analysis. In addition, data from ELISA analysis showed that the levels of fibrinolytic and plasmin factors, including thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), tissue-type plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and antithrombin III (AT III), were decreased, while those of human fibrinogen (FIB) and D-dimer (D2D) increased significantly in the co-exposure group. Moreover, the myocardial-related enzyme in serum, tested by ELISA, and cardiovascular-related protein expression of atrial natriuretic peptide and brain natriuretic peptide, tested by Western blot assay, was increased in the heart. Furthermore, the expression of inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) was increased in heart tissue subjected to combined exposure, which was manifested by Western blot assay, while the protein levels of angiotensin II (ANG II) and endothelin 1 were (ET-1) elevated in blood vessels in the co-exposure group. CONCLUSION:In conclusion, the major interactions involved in subacute toxicity due to co-exposure to low doses of SiNPs and Pb on cardiovascular system were expected to be additive and synergistic in nature. Co-exposure to SiNPs and Pb could aggravate the cardiovascular toxicity via endothelial damage, hypercoagulation, and cardiac injury in vivo.
10.2147/IJN.S185259
PEG-coated gold nanoparticles attenuate β-adrenergic receptor-mediated cardiac hypertrophy.
Qiao Yuhui,Zhu Baoling,Tian Aiju,Li Zijian
International journal of nanomedicine
Gold nanoparticles (AuNPs) are widely used as a drug delivery vehicle, which can accumulate in the heart through blood circulation. Therefore, it is very important to understand the effect of AuNPs on the heart, especially under pathological conditions. In this study, we found that PEG-coated AuNPs attenuate β-adrenergic receptor (β-AR)-mediated acute cardiac hypertrophy and inflammation. However, both isoproterenol, a non-selective β-AR agonist, and AuNPs did not induce cardiac function change or cardiac fibrosis. AuNPs exerted an anti-cardiac hypertrophy effect by decreasing β-AR expression and its downstream ERK1/2 hypertrophic pathway. Our results indicated that AuNPs might be safe and have the potential to be used as multi-functional materials (drug carrier systems and anti-cardiac hypertrophy agents).
10.2147/IJN.S130951
Detection of the Presence of Gold Nanoparticles in Organs by Transmission Electron Microscopy.
Jong Wim H De,Burger Marina C,Verheijen Marcel A,Geertsma Robert E
Materials (Basel, Switzerland)
Gold nanoparticles of 10 nm and 250 nm were intravenously injected in rats. At 24 h after administration, tissues were collected and prepared for transmission electron microscopy (TEM). In the liver and spleen of animals treated with 10 nm gold nanoparticles, groups of nanoparticles were observed that could be positively identified by Energy Dispersive X-ray (EDX) analysis to contain gold, while nanoparticles could not be detected in the heart, kidney and brain. The 10 nm gold nanoparticles were present in the phagocytic cells of the reticulo-endothelial system (RES). The 250 nm gold nanoparticles could not be detected in any of the organs investigated. Considering the number of 250 nm gold nanoparticles administered, calculations showed that it would indeed be almost impossible to detect the 250 nm gold nanoparticles in TEM preparations in view of the very low number of particles that would be theoretically present in one TEM tissue section. This shows that relatively high numbers of nanoparticles need to be administered to enable the detection of nanoparticles in organs by TEM. In a number of samples, several globular structures of approximately the expected size were found in liver cells and the endothelium of blood vessels in the brain. However, elemental analysis with EDX detection showed that these structures did not contain gold. Our studies thus indicate that the in vivo identification of nanoparticles cannot only depend on the detection of nanosized structures in cells. An additional identification of the composing elements of the nanomaterial is necessary for a positive identification of the nanomaterial.
10.3390/ma3094681
Warfarin-Capped Gold Nanoparticles: Synthesis, Cytotoxicity, and Cellular Uptake.
Leopold Loredana Florina,Rugină Dumitriţa,Oprea Ioana,Diaconeasa Zorița,Leopold Nicolae,Suciu Maria,Coman Vasile,Vodnar Dan Cristian,Pintea Adela,Coman Cristina
Molecules (Basel, Switzerland)
Currently, research studies on nanoparticle cytotoxicity, uptake or internalization into the body's cells are of great interest for the improvement of diagnostic and therapeutic applications. We report here the synthesis and characterization of very stable novel warfarin-capped gold nanoparticles with an average diameter of 54 ± 10 nm which were prepared using sodium warfarin as a reducing agent. The nanoparticles were tested in terms of cytotoxicity and cellular internalization in vitro on two cell lines: normal lung fibroblast HFL-1 and human retinal pigment epithelial D407 cells. Our results showed that the normal lung fibroblast HFL-1 cells were more sensitive to the nanoparticle treatment compared to the human retinal pigment epithelial D407 cells. Moreover, any signs of potential cytotoxicity occurred during the first 24 h of treatment, the cellular viability remaining largely unchanged for longer exposure times. Transmission electron microscopy and dark field hyperspectral imaging revealed that the nanoparticles were effectively delivered and released to the HFL-1 and D407 cells' cytoplasm. Our results provide valuable information to further investigate sodium warfarin-capped gold nanoparticles for possible biological applications.
10.3390/molecules24224145
Nanoparticles with High-Surface Negative-Charge Density Disturb the Metabolism of Low-Density Lipoprotein in Cells.
Bai Xue,Zhang Jiaxin,Chang Ya-Nan,Gu Weihong,Lei Runhong,Qin Yanxia,Xia Shibo,Ma Sihan,Liang Yuelan,Chen Kui,Li Juan,Sun Baoyun,Xing Gengmei
International journal of molecular sciences
Endocytosis is an important pathway to regulate the metabolism of low-density lipoprotein (LDL) in cells. At the same time, engineering nanoparticles (ENPs) enter the cell through endocytosis in biomedical applications. Therefore, a crucial question is whether the nanoparticles involved in endocytosis could impact the natural metabolism of LDL in cells. In this study, we fabricated a series of gold nanoparticles (AuNPs) (13.00 ± 0.69 nm) with varied surface charge densities. The internalized AuNPs with high-surface negative-charge densities (HSNCD) significantly reduced LDL uptake in HepG-2, HeLa, and SMMC-7721 cells compared with those cells in control group. Notably, the significant reduction of LDL uptake in cells correlates with the reduction of LDL receptors (LDL-R) on the cell surface, but there is no change in protein and mRNA of LDL-Rs. The cyclic utilization of LDL-R in cells is a crucial pathway to maintain the homoeostasis of LDL uptake. The release of LDL-Rs from LDL/LDL-R complexes in endosomes depended on reduction of the pH in the lumen. AuNPs with HSNCD hampered vacuolar-type H⁺-ATPase V1 (ATPaseV1) and ATPaseV0 binding on the endosome membrane, blocking protons to enter the endosome by the pump. Hence, fewer freed LDL-Rs were transported into recycling endosomes (REs) to be returned to cell surface for reuse, reducing the LDL uptake of cells by receptor-mediated endocytosis. The restrained LDL-Rs in the LDL/LDL-R complex were degraded in lysosomes.
10.3390/ijms19092790
Biomimetic gold nanoparticles for its cytotoxicity and biocompatibility evidenced by fluorescence-based assays in cancer (MDA-MB-231) and non-cancerous (HEK-293) cells.
Jeyarani Samynathan,Vinita Nadar Manimaran,Puja Patel,Senthamilselvi Singaravelu,Devan Umapathy,Velangani Antony Joseph,Biruntha Muniyandi,Pugazhendhi Arivalagan,Kumar Ponnuchamy
Journal of photochemistry and photobiology. B, Biology
Biomimetic gold nanoparticles of biological origin have created a significant impact on the field of biomedicine due to the great expectations of its applications. Because of this, the influences of biomimetic gold nanoparticles have been immensely studied, targeting various cancer cells. However, the impact of biomimetic gold nanoparticles against normal non-cancerous cells is scanty, which impose several limitations in their utility. Taking this as a challenge, we in this study report the biomimetic gold nanoparticles from marine seaweed Gelidium pusillum (G. pusillum) to evaluate its cytotoxic and biocompatible ability evidenced by fluorescence-based assays in cultured cells. The gold nanoparticles obtained in the study were spherical shaped with a mean diameter of 12 ± 4.2 nm. The seaweed extract plays a crucial role in stabilizing the gold nanoparticles to avoid aggregation and coalescence. At an IC concentration of 43.09 ± 1.6 μgmL, the biomimetic gold nanoparticles were found to be toxic to cancerous cells (MDA-MB-231). Whereas, biomimetic gold nanoparticles exhibit significant biocompatibility with human embryonic kidney cells even at a higher concentration of 150 μgmL. The morphological based fluorescence assays confirmed the ability of biomimetic gold nanoparticles in inducing apoptosis and thereby kills cancer cells. Altogether, the gold nanoparticles were safe to normal cells and did not show a significant impact. Hence, the novel biomimetic gold nanoparticles hold potential as multifaceted agent and can further be taken up to various biomedical applications.
10.1016/j.jphotobiol.2019.111715
Surface chemistry governs the sub-organ transfer, clearance and toxicity of functional gold nanoparticles in the liver and kidney.
Li Xue,Wang Bing,Zhou Shuang,Chen Wei,Chen Hanqing,Liang Shanshan,Zheng Lingna,Yu Hongyang,Chu Runxuan,Wang Meng,Chai Zhifang,Feng Weiyue
Journal of nanobiotechnology
BACKGROUND:To effectively applied nanomaterials (NMs) in medicine, one of the top priorities is to address a better understanding of the possible sub-organ transfer, clearance routes, and potential toxicity of the NMs in the liver and kidney. RESULTS:Here we explored how the surface chemistry of polyethylene glycol (PEG), chitosan (CS), and polyethylenimine (PEI) capped gold nanoparticles (GNPs) governs their sub-organ biodistribution, transfer, and clearance profiles in the liver and kidney after intravenous injection in mice. The PEG-GNPs maintained dispersion properties in vivo, facilitating passage through the liver sinusoidal endothelium and Disse space, and were captured by hepatocytes and eliminated via the hepatobiliary route. While, the agglomeration/aggregation of CS-GNPs and PEI-GNPs in hepatic Kupffer and endothelial cells led to their long-term accumulation, impeding their elimination. The gene microarray analysis shows that the accumulation of CS-GNPs and PEI-GNPs in the liver induced obvious down-regulation of Cyp4a or Cyp2b related genes, suggesting CS-GNP and PEI-GNP treatment impacted metabolic processes, while the PEI-GNP treatment is related with immune responses. CONCLUSIONS:This study demonstrates that manipulation of nanoparticle surface chemistry can help NPs selectively access distinct cell types and elimination pathways, which help to clinical potential of non-biodegradable NPs.
10.1186/s12951-020-00599-1
Gold nanoparticles synthesized from Euphorbia fischeriana root by green route method alleviates the isoprenaline hydrochloride induced myocardial infarction in rats.
Zhang Tipeng,Dang Minyan,Zhang Wenzhi,Lin Xue
Journal of photochemistry and photobiology. B, Biology
The procurance of gold nanoparticles in the plant extracts is an excellent way to attain nanomaterials natural and eco-friendly nanomaterials. The Dehydrated roots of Chinese Euphorbia fischeriana flowering plant are called "Lang-Du". In this study, the retrieving of gold nanoparticles from Euphorbia fischeriana root was amalgamated by standard procedure. Fabricated gold nanoparticles were portrayed through the investigations of ultraviolet and visible spectrophotometry (UV-Vis), Fourier transform infrared spectroscopy (FTIR), High resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The UV-Vis and FTIR results explicated the obtained particles were sphere-shaped and the terpenoids of Euphorbia fischeriana had strong communications with gold surface. The HRTEM and XRD images exposed the produced gold nanoparticles had an extreme composition of crystal arrangement and excellent uniformed size of particles. In our study, the Isoprenaline induced myocardial damage established the elevation in TBARS, LOOH of heart tissues and notable decline in antioxidant enzymes SOD, CAT, GPx, and GSH. This biochemical result was additionally proved by histopathological assessment. Remarkably, the pretreatment with EF-AuNps(50 mg/kg b.w) illustrated stabilized levels of serum creatine and cardiotropins in myocardial infarcted animals. And further we understood the essential function of NF-ƙB, TNF-α, IL-6 signaling molecules and its way progression in the development of vascular tenderness.
10.1016/j.jphotobiol.2019.111705
Antibacterial mechanism of gold nanoparticles on Streptococcus pneumoniae.
Ortiz-Benítez Edgar Augusto,Velázquez-Guadarrama Norma,Durán Figueroa Noé Valentín,Quezada Héctor,Olivares-Trejo José de Jesús
Metallomics : integrated biometal science
Streptococcus pneumoniae is a causal agent of otitis media, pneumonia, meningitis and severe cases of septicemia. This human pathogen infects elderly people and children with a high mortality rate of approximately one million deaths per year worldwide. Antibiotic-resistance of S. pneumoniae strains is an increasingly serious health problem; therefore, new therapies capable of combating pneumococcal infections are indispensable. The application of gold nanoparticles has emerged as an option in the control of bacterial infections; however, the mechanism responsible for bacterial cell lysis remains unclear. Specifically, it has been observed that gold nanoparticles are capable of crossing different structures of the S. pneumoniae cells, reaching the cytosol where inclusion bodies of gold nanoparticles are noticed. In this work, a novel process for the separation of such inclusion bodies that allowed the analysis of the biomolecules such as carbohydrates, lipids and proteins associated with the gold nanoparticles was developed. Then, it was possible to separate and identify proteins associated with the gold nanoparticles, which were suggested as possible candidates that facilitate the interaction and entry of gold nanoparticles into S. pneumoniae cells.
10.1039/c9mt00084d
Green synthesis of gold nanoparticles using a extract and their antiproliferative effect in liver cancer cells (HepG2).
Ji Yujiang,Cao Yang,Song Yong
Artificial cells, nanomedicine, and biotechnology
Hepatocellular carcinoma is the most common liver cancer among different types of cancers. mushroom species traditionally used as an alternative medicine in china for centuries. Gold nanoparticles plays vital role in the development of the anticancer drugs. In our research, we investigated the gold nanoparticles with on the hepatocellular carcinoma HepG2 cells. The synthesized gold nanoparticles stability and integrity was studied at different time intervals. The gold nanoparticles potentially halt the growth of the HepG2 cells at the IC50 concentration between 10 μg and 12.5 μg/ml. The HR-TEM and XRD revealed the size and shape of the synthesized gold nanoparticles. The size of the gold nanoparticles was about 15 20 nm and the shape of gold nanoparticles was face-center-cubic structure. The FT-IR results proved that the gold nanoparticles contain hydroxyl and alkynes groups. The gold nanoparticles extract develops ROS and cause damage to the mitochondrial membrane potential in the hepatocellular carcinoma HepG2 cells. The gold nanoparticles extract tends to initiate the apoptosis by activating the Bax, Bid, caspases and inhibits the activation anti-apoptotic bcl-2 in the HepG2 cells. Our results concluded that the gold nanoparticles with would be an efficient chemotherapeutic drug against the hepatocellular carcinoma cells.
10.1080/21691401.2019.1629952
Unexpected intracellular biodegradation and recrystallization of gold nanoparticles.
Balfourier Alice,Luciani Nathalie,Wang Guillaume,Lelong Gerald,Ersen Ovidiu,Khelfa Abdelali,Alloyeau Damien,Gazeau Florence,Carn Florent
Proceedings of the National Academy of Sciences of the United States of America
Gold nanoparticles are used in an expanding spectrum of biomedical applications. However, little is known about their long-term fate in the organism as it is generally admitted that the inertness of gold nanoparticles prevents their biodegradation. In this work, the biotransformations of gold nanoparticles captured by primary fibroblasts were monitored during up to 6 mo. The combination of electron microscopy imaging and transcriptomics study reveals an unexpected 2-step process of biotransformation. First, there is the degradation of gold nanoparticles, with faster disappearance of the smallest size. This degradation is mediated by NADPH oxidase that produces highly oxidizing reactive oxygen species in the lysosome combined with a cell-protective expression of the nuclear factor, erythroid 2. Second, a gold recrystallization process generates biomineralized nanostructures consisting of 2.5-nm crystalline particles self-assembled into nanoleaves. Metallothioneins are strongly suspected to participate in buildings blocks biomineralization that self-assembles in a process that could be affected by a chelating agent. These degradation products are similar to aurosomes structures revealed 50 y ago in vivo after gold salt therapy. Overall, we bring to light steps in the lifecycle of gold nanoparticles in which cellular pathways are partially shared with ionic gold, revealing a common gold metabolism.
10.1073/pnas.1911734116
Electroanalysis on an Interdigitated Electrode for High-Affinity Cardiac Troponin I Biomarker Detection by Aptamer-Gold Conjugates.
ACS omega
The primary reasons for myocardial infarction (MI) are pericarditis, arrhythmia, and heart failure, causing predominant deaths worldwide. Patients need a potential diagnostic system and treatment before cardiomyocyte damage. Cardiac biomarkers are released from myocytes immediately after a heart attack. Troponin is an efficient biomarker released from dead cells within a few hours. Aptamers are artificial antibodies used effectively in the biosensor field for biomarker detection. Along with aptamers, the application of nanomaterials is also expected to enhance the detection limits of biosensors. In this investigation, selected aptamers against cardiac troponin I (cTnI) were conjugated with gold nanoparticles (GNPs) to diagnose MI and compared with an aptamer-only control group on an interdigitated electrode surface. Based on electroanalysis, cTnI was detected at concentrations as low as 1 fM, and the detection limit improved to 100 aM when the aptamer was conjugated with GNP. In addition, aptamer-GNP conjugates increased the current level at the tested concentrations of cTnI. Control experiments with noncomplementary aptamers and relevant proteins did not result in notable changes in the current, demonstrating the selective detection of cTnI.
10.1021/acsomega.0c03260
Influence of Size and Shape on the Anatomical Distribution of Endotoxin-Free Gold Nanoparticles.
Talamini Laura,Violatto Martina B,Cai Qi,Monopoli Marco P,Kantner Karsten,Krpetić Željka,Perez-Potti André,Cookman Jennifer,Garry David,P Silveira Camila,Boselli Luca,Pelaz Beatriz,Serchi Tommaso,Cambier Sébastien,Gutleb Arno C,Feliu Neus,Yan Yan,Salmona Mario,Parak Wolfgang J,Dawson Kenneth A,Bigini Paolo
ACS nano
The transport and the delivery of drugs through nanocarriers is a great challenge of pharmacology. Since the production of liposomes to reduce the toxicity of doxorubicin in patients, a plethora of nanomaterials have been produced and characterized. Although it is widely known that elementary properties of nanomaterials influence their in vivo kinetics, such interaction is often poorly investigated in many preclinical studies. The present study aims to evaluate the actual effect of size and shape on the biodistribution of a set of gold nanoparticles (GNPs) after intravenous administration in mice. To this goal, quantitative data achieved by inductively coupled plasma mass spectrometry and observational results emerging from histochemistry (autometallography and enhanced dark-field hyperspectral microscopy) were combined. Since the immune system plays a role in bionano-interaction we used healthy immune-competent mice. To keep the immune surveillance on the physiological levels we synthesized endotoxin-free GNPs to be tested in specific pathogen-free animals. Our study mainly reveals that (a) the size and the shape greatly influence the kinetics of accumulation and excretion of GNPs in filter organs; (b) spherical and star-like GNPs showed the same percentage of accumulation, but a different localization in liver; (c) only star-like GNPs are able to accumulate in lung; (d) changes in the geometry did not improve the passage of the blood brain barrier. Overall, this study can be considered as a reliable starting point to drive the synthesis and the functionalization of potential candidates for theranostic purposes in many fields of research.
10.1021/acsnano.7b00497