Erythrocyte membrane coated with nitrogen-doped quantum dots and polydopamine composite nano-system combined with photothermal treatment of Alzheimer's disease.
Journal of colloid and interface science
Mitochondrial dysfunction and metal ion imbalance are recognized as pathological hallmarks of Alzheimer's Disease (AD), leading to deposition of β-amyloid (Aβ) thereby and inducing neurotoxicity, activating apoptosis, eliciting oxidative stress, and ultimately leading to cognitive impairment. In this study, the red blood cell membrane (RBC) was used as a vehicle for encapsulating carbon quantum dots (CQD) and polydopamine (PDA), creating a nanocomposite (PDA-CQD/RBC). This nanocomposite was combined with near-infrared light (NIR) for AD treatment. The RBC offers anti-immunorecognition properties to evade immune clearance, PDA exhibits enzyme-mimicking activity to mitigate oxidative stress damage, and CQD acts as a chelating agent for metal ions (Cu), effectively preventing Cu-mediated aggregation of Aβ. Furthermore, the local heating induced by near-infrared laser irradiation can dismantle the formed Aβ fibers and enhance the blood-brain barrier's permeability. Both in vitro and animal experiments have shown that PDA-CQD/RBC, in combination with NIR, mitigates neuroinflammation, and ameliorates behavioral deficits in mice. This approach targets multiple pathological pathways, surpassing the limitations of single-target treatments and enhancing therapeutic efficacy while decelerating disease progression.
10.1016/j.jcis.2024.02.219
Faulty autolysosome acidification in Alzheimer's disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques.
Nature neuroscience
Autophagy is markedly impaired in Alzheimer's disease (AD). Here we reveal unique autophagy dysregulation within neurons in five AD mouse models in vivo and identify its basis using a neuron-specific transgenic mRFP-eGFP-LC3 probe of autophagy and pH, multiplex confocal imaging and correlative light electron microscopy. Autolysosome acidification declines in neurons well before extracellular amyloid deposition, associated with markedly lowered vATPase activity and build-up of Aβ/APP-βCTF selectively within enlarged de-acidified autolysosomes. In more compromised yet still intact neurons, profuse Aβ-positive autophagic vacuoles (AVs) pack into large membrane blebs forming flower-like perikaryal rosettes. This unique pattern, termed PANTHOS (poisonous anthos (flower)), is also present in AD brains. Additional AVs coalesce into peri-nuclear networks of membrane tubules where fibrillar β-amyloid accumulates intraluminally. Lysosomal membrane permeabilization, cathepsin release and lysosomal cell death ensue, accompanied by microglial invasion. Quantitative analyses confirm that individual neurons exhibiting PANTHOS are the principal source of senile plaques in amyloid precursor protein AD models.
10.1038/s41593-022-01084-8
Molecular insights into nanoplastics-peptides binding and their interactions with the lipid membrane.
Biophysical chemistry
Micro- and nanoplastics have become a significant concern, due to their ubiquitous presence in the environment. These particles can be internalized by the human body through ingestion, inhalation, or dermal contact, and then they can interact with environmental or biological molecules, such as proteins, resulting in the formation of the protein corona. However, information on the role of protein corona in the human body is still missing. Coarse-grain models of the nanoplastics and pentapeptides were created and simulated at the microscale to study the role of protein corona. Additionally, a lipid bilayer coarse-grain model was reproduced to investigate the behavior of the coronated nanoplastics in proximity of a lipid bilayer. Hydrophobic and aromatic amino acids have a high tendency to create stable bonds with all nanoplastics. Moreover, polystyrene and polypropylene establish bonds with polar and charged amino acids. When the coronated nanoplastics are close to a lipid bilayer, different behaviors can be observed. Polyethylene creates a single polymeric chain, while polypropylene tends to break down into its single chains. Polystyrene can both separate into its individual chains and remain aggregated. The protein corona plays an important role when interacting with the nanoplastics and the lipid membrane. More studies are needed to validate the results and to enhance the complexity of the systems.
10.1016/j.bpc.2024.107213
Bioeffects of Inhaled Nanoplastics on Neurons and Alteration of Animal Behaviors through Deposition in the Brain.
Liu Xiaoyan,Zhao Yingcan,Dou Jiabin,Hou Qinghong,Cheng Jinxiong,Jiang Xingyu
Nano letters
The potential toxicity of nanoplastics on plants has previously been illustrated, but whether nanoplastics could cause neurotoxicity, especially to higher animals, remains unclear. We now demonstrate that nanoplastics can be deposited in the brain via nasal inhalation, triggering neuron toxicity and altering the animal behavior. Polystyrene nanoparticles (PS-NPs) of PS-COOH and PS-NH are used as models for nanoplastics. We designed a microfluidic chip to evaluate the PS-NPs with different concentrations, surface ligands, and sizes to interact with neurons. Smaller PS-NPs can induce more cellular uptake than larger PS-NPs. PS-NPs with a size of 80 nm can reach and deposit in the brain of mice via aerosol inhalation. Mice inhaling PS-NPs exhibit fewer activities in comparison to those inhaling water droplets. An obvious neurotoxicity of the nanoplastics could be observed from the results of the inhibition of AChE activities. Our results show the potential significance of the physiochemical properties of organic nanoplastics on depositing in mammalian brains by nasal inhalation.
10.1021/acs.nanolett.1c04184
Nanotheranostics: Congo Red/Rutin-MNPs with Enhanced Magnetic Resonance Imaging and H2O2-Responsive Therapy of Alzheimer's Disease in APPswe/PS1dE9 Transgenic Mice.
Hu Bingbing,Dai Fengying,Fan Zhanming,Ma Guanghui,Tang Qunwei,Zhang Xin
Advanced materials (Deerfield Beach, Fla.)
As nanotheranostics, Congo red/Rutin-MNPs combine the abilities of diagnosis and treatment of Alzheimer's disease (AD). The biocompatible nanotheranostics system based on iron oxide magnetic nanoparticles, with ultrasmall size and excellent magnetic properties, can specifically detect amyloid plaques by magnetic resonance imaging, realize targeted delivery of AD therapeutic agents, achieve drug controlled release by H2O2 response, and prevent oxidative stress.
10.1002/adma.201502227
Unexpected Function of a Heptapeptide-Conjugated Zwitterionic Polymer that Coassembles into β-Amyloid Fibrils and Eliminates the Amyloid Cytotoxicity.
Wang Wenjuan,Zhao Guangfu,Dong Xiaoyan,Sun Yan
ACS applied materials & interfaces
Fibrillogenesis of amyloid β-protein (Aβ) is pathologically associated with Alzheimer's disease (AD), so modulating Aβ aggregation is crucial for AD prevention and treatment. Herein, a zwitterionic polymer with short dimethyl side chains (pID) is synthesized and conjugated with a heptapeptide inhibitor (Ac-LVFFARK-NH, LK7) to construct zwitterionic polymer-inhibitor conjugates for enhanced inhibition of Aβ aggregation. However, it is unexpectedly found that the LK7@pID conjugates remarkably promote Aβ fibrillization to form more fibrils than the free Aβ system but effectively eliminate Aβ-induced cytotoxicity. Such an unusual behavior of the LK7@pID conjugates is unraveled by extensive mechanistic studies. First, the hydrophobic environment within the assembled micelles of LK7@pID promotes the hydrophobic interaction between Aβ molecules and LK7@pID, which triggers Aβ aggregation at the very beginning, making fibrillization occur at an earlier stage. Second, in the aggregation process, the LK7@pID micelles disassemble by the intensive interactions with Aβ, and LK7@pID participates in the fibrillization by being embedded in the Aβ fibrils, leading to the formation of hybrid and heterogeneous fibrillar aggregates with a different structure than normal Aβ fibrils. This unique Trojan horse-like feature of LK7@pID conjugates has not been observed for any other inhibitors reported previously and may shed light on the design of new modulators against β-amyloid cytotoxicity.
10.1021/acsami.1c01132
Mind over Microplastics: Exploring Microplastic-Induced Gut Disruption and Gut-Brain-Axis Consequences.
Current issues in molecular biology
As environmental plastic waste degrades, it creates an abundance of diverse microplastic particles. Consequently, microplastics contaminate drinking water and many staple food products, meaning the oral ingestion of microplastics is an important exposure route for the human population. Microplastics have long been considered inert, however their ability to promote microbial dysbiosis as well as gut inflammation and dysfunction suggests they are more noxious than first thought. More alarmingly, there is evidence for microplastics permeating from the gut throughout the body, with adverse effects on the immune and nervous systems. Coupled with the now-accepted role of the gut-brain axis in neurodegeneration, these findings support the hypothesis that this ubiquitous environmental pollutant is contributing to the rising incidence of neurodegenerative diseases, like Alzheimer's disease and Parkinson's disease. This comprehensive narrative review explores the consequences of oral microplastic exposure on the gut-brain-axis by considering current evidence for gastrointestinal uptake and disruption, immune activation, translocation throughout the body, and neurological effects. As microplastics are now a permanent feature of the global environment, understanding their effects on the gut, brain, and whole body will facilitate critical further research and inform policy changes aimed at reducing any adverse consequences.
10.3390/cimb46050256
The Therapeutic Benefits of Intravenously Administrated Nanoparticles in Stroke and Age-related Neurodegenerative Diseases.
Current pharmaceutical design
The mean global lifetime risk of neurological disorders such as stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) has shown a large effect on economy and society. Researchers are still struggling to find effective drugs to treat neurological disorders and drug delivery through the blood-brain barrier (BBB) is a major challenge to be overcome. The BBB is a specialized multicellular barrier between peripheral blood circulation and neural tissue. Unique and selective features of the BBB allow it to tightly control brain homeostasis as well as the movement of ions and molecules. Failure in maintaining any of these substances causes BBB breakdown and subsequently enhances neuroinflammation and neurodegeneration. BBB disruption is evident in many neurological conditions. Nevertheless, the majority of currently available therapies have tremendous problems with drug delivery into the impaired brain. Nanoparticle (NP)-mediated drug delivery has been considered a profound substitute to solve this problem. NPs are colloidal systems with a size range of 1-1000 nm which can encapsulate therapeutic payloads, improve drug passage across the BBB, and target specific brain areas in neurodegenerative/ischemic diseases. A wide variety of NPs has been displayed for the efficient brain delivery of therapeutics via intravenous administration, especially when their surfaces are coated with targeting moieties. Here, we discuss recent advances in the development of NP-based therapeutics for the treatment of stroke, PD, and AD, as well as the factors affecting their efficacy after systemic administration.
10.2174/1381612828666220608093639
Adverse Effects of Non-Metallic Nanoparticles in the Central Nervous System.
Materials (Basel, Switzerland)
The interest in nanoparticles (NPs) and their effects on living organisms has been continuously growing in the last decades. A special interest is focused on the effects of NPs on the central nervous system (CNS), which seems to be the most vulnerable to their adverse effects. Non-metallic NPs seem to be less toxic than metallic ones; thus, the application of non-metallic NPs in medicine and industry is growing very fast. Hence, a closer look at the impact of non-metallic NPs on neural tissue is necessary, especially in the context of the increasing prevalence of neurodegenerative diseases. In this review, we summarize the current knowledge of the in vitro and in vivo neurotoxicity of non-metallic NPs, as well as the mechanisms associated with negative or positive effects of non-metallic NPs on the CNS.
10.3390/ma16237264