Immune Profiling and Multiplexed Label-Free Detection of 2D MXenes by Mass Cytometry and High-Dimensional Imaging.
Advanced materials (Deerfield Beach, Fla.)
There is a critical unmet need to detect and image 2D materials within single cells and tissues while surveying a high degree of information from single cells. Here, a versatile multiplexed label-free single-cell detection strategy is proposed based on single-cell mass cytometry by time-of-flight (CyTOF) and ion-beam imaging by time-of-flight (MIBI-TOF). This strategy, "Label-free sINgle-cell tracKing of 2D matErials by mass cytometry and MIBI-TOF Design" (LINKED), enables nanomaterial detection and simultaneous measurement of multiple cell and tissue features. As a proof of concept, a set of 2D materials, transition metal carbides, nitrides, and carbonitrides (MXenes), is selected to ensure mass detection within the cytometry range while avoiding overlap with more than 70 currently available tags, each able to survey multiple biological parameters. First, their detection and quantification in 15 primary human immune cell subpopulations are demonstrated. Together with the detection, mass cytometry is used to capture several biological aspects of MXenes, such as their biocompatibility and cytokine production after their uptake. Through enzymatic labeling, MXenes' mediation of cell-cell interactions is simultaneously evaluated. In vivo biodistribution experiments using a mixture of MXenes in mice confirm the versatility of the detection strategy and reveal MXene accumulation in the liver, blood, spleen, lungs, and relative immune cell subtypes. Finally, MIBI-TOF is applied to detect MXenes in different organs revealing their spatial distribution. The label-free detection of 2D materials by mass cytometry at the single-cell level, on multiple cell subpopulations and in multiple organs simultaneously, will enable exciting new opportunities in biomedicine.
10.1002/adma.202205154
Preparation of a disposable electrochemiluminescence sensor chip based on an MXene-loaded ruthenium luminescent agent and its application in the detection of carcinoembryonic antigens.
The Analyst
Carcinoembryonic antigen (CEA) is an important cancer marker that plays a significant role in achieving low-cost, rapid and highly sensitive clinical detection. In this work, we developed a disposable electrochemiluminescence (ECL) sensor chip based on a screen-printed electrode (SPE) for detecting CEA ECL technology. An amino-modified TiC MXene was used as a carrier to successfully prepare a highly efficient ECL probe AuNPs-Ru-Arg@NH-TiC-MXene by loading with AuNPs-Arg through covalent links and modifying with a ruthenium complex. Upon the addition of CEA, the ECL signal decreased significantly with the increase of CEA, due to the formation of immune complexes at the interface of the electrode. The sensing chip was used to detect CEA in an aqueous solution and found to have a detection limit of 1.5 pg mL. The chip was used to determine CEA in the serum of healthy humans and cancer patients, and the results were consistent with those obtained using ELISA. The disposable ECL sensor chip has many advantages including convenience, rapid detection, low cost and easy mass production; thus it has great application potential in clinical cancer diagnosis.
10.1039/d2an00450j
A TiC-MXene-functionalized LRSPR biosensor based on sandwich amplification for human IgG detection.
Zhao Xueqi,Zhang Yue,Wang Xinghua,Ma Pinyi,Song Daqian,Sun Ying
Analytical and bioanalytical chemistry
Long-range surface plasmon resonance (LRSPR) has demonstrated excellent performance in sensing and detection, due to its higher accuracy and sensitivity compared with conventional surface plasmon resonance (cSPR). In this work, we establish an LRSPR biosensor which employs PDA/TiC-MXene/PDA-gold film as a sensing substrate and gold nanoparticles (AuNPs) as enhancers. TiC-MXene is an emerging two-dimensional (2D) layered material which is used extensively in immunoassay and biosensing. The sensing substrate comprises two polydopamine (PDA) films between which is sandwiched a TiC-MXene film based on a gold film, which provides a large surface area and abundant binding sites to rabbit anti-human IgG (Ab). Sandwich amplification is adopted to enhance the sensitivity of the LRSPR biosensor, and AuNPs/staphylococcal protein A (SPA)/mouse anti-human IgG (Ab) composites are introduced into the flow cell as enhancers after the immune binding of human IgG to Ab. The antigen (human IgG) detection range is 0.075 μg mL to 40 μg mL, and the limit of detection is almost 20 times lower than that for cSPR biosensors. This novel LRSPR biosensor demonstrates excellent performance in immune sensing over a broad detection range and a low limit of detection. Subsequent modification of the LRSPR sensing platform could be made for extensive application in various biological detection fields.
10.1007/s00216-021-03858-8
Programmable dual-electric-field immunosensor using MXene-Au-based competitive signal probe for natural parathion-methyl detection.
Biosensors & bioelectronics
Immunosensor is a promising tool for natural parathion-methyl (PTM) detection, and its analytical advantages can be magnified by introducing flexibly-fabricating technique. Herein, we present a dual-electric-field PTM immunosensor on highly-compatible screen-printed electrode (SPE). MXene-Au, the product of in-situ gold nanoparticle growth on MXene, provides considerable binding sites for PTM antigen (ATG) and methylene blue (MB). During sensing, the MXene-Au-MB-ATG probe competitively binds antibody against PTM, composing a ratiometric immune-system. With DC-biased sine excitations from complementary waveforms, on-chip electric field couple improves immunoreactions among PTM, probe, and antibody. Electric field distribution is programmed by trimming bypass resistors to pursue optimal performance. Probe synthesis is solidly proven with morphological examinations, and competition mechanism between the probe and target PTM is clarified in electrochemical analyses. Remarkably, this method brings less consumption of immune time than electric-field-free or solo-electric-field setup (50 s vs. 900 or 70 s), and simultaneously provides more powerful ratiometric signal than the rivals. Log-linear relationship, between PTM level and sensor readout, is established in 0.02-38 ng/mL, and limit of detection is found as 0.01 ng/mL. This method is applied in laboratorial and natural PTM analyses, and the readouts are consistent with high performance liquid chromatography and recovery test.
10.1016/j.bios.2022.114546
A MXene-Based Bionic Cascaded-Enzyme Nanoreactor for Tumor Phototherapy/Enzyme Dynamic Therapy and Hypoxia-Activated Chemotherapy.
Nano-micro letters
The enzyme-mediated elevation of reactive oxygen species (ROS) at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment. Herein, we proposed a camouflaged bionic cascaded-enzyme nanoreactor based on TiC nanosheets for combined tumor enzyme dynamic therapy (EDT), phototherapy and deoxygenation-activated chemotherapy. Briefly, glucose oxidase (GOX) and chloroperoxidase (CPO) were chemically conjugated onto TiC nanosheets, where the deoxygenation-activated drug tirapazamine (TPZ) was also loaded, and the TiC-GOX-CPO/TPZ (TGCT) was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47 (mTGCT). Due to biomimetic membrane camouflage and CD47 overexpression, mTGCT exhibited superior immune escape and homologous targeting capacities, which could effectively enhance the tumor preferential targeting and internalization. Once internalized into tumor cells, the cascade reaction of GOX and CPO could generate HClO for efficient EDT. Simultaneously, additional laser irradiation could accelerate the enzymic-catalytic reaction rate and increase the generation of singlet oxygen (O). Furthermore, local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy. Consequently, mTGCT exhibits amplified synergistic therapeutic effects of tumor phototherapy, EDT and chemotherapy for efficient tumor inhibition. This intelligent cascaded-enzyme nanoreactor provides a promising approach to achieve concurrent and significant antitumor therapy.
10.1007/s40820-021-00761-w
Skeletal muscle regeneration with 3D bioprinted hyaluronate/gelatin hydrogels incorporating MXene nanoparticles.
International journal of biological macromolecules
There has been significant progress in the field of three-dimensional (3D) bioprinting technology, leading to active research on creating bioinks capable of producing structurally and functionally tissue-mimetic constructs. TiCT MXene nanoparticles (NPs), promising two-dimensional nanomaterials, are being investigated for their potential in muscle regeneration due to their unique physicochemical properties. In this study, we integrated MXene NPs into composite hydrogels made of gelatin methacryloyl (GelMA) and hyaluronic acid methacryloyl (HAMA) to develop bioinks (namely, GHM bioink) that promote myogenesis. The prepared GHM bioinks were found to offer excellent printability with structural integrity, cytocompatibility, and microporosity. Additionally, MXene NPs within the 3D bioprinted constructs encouraged the differentiation of C2C12 cells into skeletal muscle cells without additional support of myogenic agents. Genetic analysis indicated that representative myogenic markers both for early and late myogenesis were significantly up-regulated. Moreover, animal studies demonstrated that GHM bioinks contributed to enhanced regeneration of skeletal muscle while reducing immune responses in mice models with volumetric muscle loss (VML). Our results suggest that the GHM hydrogel can be exploited to craft a range of strategies for the development of a novel bioink to facilitate skeletal muscle regeneration because these MXene-incorporated composite materials have the potential to promote myogenesis.
10.1016/j.ijbiomac.2024.130696