Composite organic-inorganic nanoparticles (COINs) are novel optical labels for detection of biomolecules. We have previously developed methods to encapsulate COINs and to functionalize them with antibodies. Here we report the first steps toward application of COINs to the detection of proteins in human tissues. Two analytes, PSA and CK18, are detected simultaneously using two different COINs in a direct binding assay, and two different COINs are shown to simultaneously label PSA in tissue samples.
BackgroundDetection of single cell epitopes has been a mainstay of immunophenotyping for over three decades, primarily using fluorescence techniques for quantitation. Fluorescence has broad overlapping spectra, limiting multiplexing abilities.Methodology/Principal FindingsTo expand upon current detection systems, we developed a novel method for multi-color immuno-detection in single cells using “Composite Organic-Inorganic Nanoparticles” (COINs) Raman nanoparticles. COINs are Surface-Enhanced Raman Scattering (SERS) nanoparticles, with unique Raman spectra. To measure Raman spectra in single cells, we constructed an automated, compact, low noise and sensitive Raman microscopy device (Integrated Raman BioAnalyzer). Using this technology, we detected proteins expressed on the surface in single cells that distinguish T-cells among human blood cells. Finally, we measured intracellular phosphorylation of Stat1 (Y701) and Stat6 (Y641), with results comparable to flow cytometry.Conclusions/SignificanceThus, we have demonstrated the practicality of applying COIN nanoparticles for measuring intracellular phosphorylation, offering new possibilities to expand on the current fluorescent technology used for immunoassays in single cells.
The therapeutic efficiency of reactive oxygen species (ROS)‐based nanotherapeutics is restrained by the rigorous production conditions of relatively sufficient and kinetically matching supply of intracellular substrates. The cumulative disruption of redox homeostasis and consequent pathology (e.g., Parkinson's disease) with low levels of substrates in living organisms may provide a promising model for ROS‐based therapy. Herein, a catechol chemistry‐mediated ternary nanostructure is prepared for long‐lasting generation of oxidative •OH in weakly acidic, low H2O2 homeostasis conditions of tumor. This platform employs mesoporous polydopamine (MPDA) as the porous redox mediator, while PDA‐induced sequential precipitation and biomineralization lead to hydroxy iron oxide (FeOOH) as the “iron reservoir,” and calcium phosphate (CaP) as the pH‐sensitive sheddable shell. In weakly acidic conditions, the CaP layer can be degraded to expose the catalytic surface of Fe‐dopamine interplay, where FeOOH dissolution, Fe(III) chelation, Fe(III) reduction, Fe(II) release take place sequentially and continuously for Fe(II) recycling and Fenton catalysis. Both in vitro and in vivo studies verify the significant inhibition of cancer cells and tumor regression, which can also be strengthened by the local photothermal heating. This work establishes the first paradigm of pathologically inspired nanohybrids of ROS generators with long‐lasting efficacy for cancer therapy.
The use of reactive oxygen species (ROS) generators based on singleatom catalysts (SACs) has been an emerging strategy for mediating tumor therapy, however, the current systems suffer from low mass transport efficiency. Here, a novel strategy of morphology fragmentation is developed to fabricate flower-like SAC nanozymes with greatly improved 3D accessibility of active sites. Specifically, the coordinationally polymerized zeolite imidazole framework acts as a polyphenol oxidase-like enzyme to catalyze the in situ polymerization of polydopamine (PDA) which leads to blockage of micropores and crosslinking of the morphologydeteriorated ZIF nanosheets. The protective carbonization by PDA results in SAC nanozymes (C-NFs) with plenty of reopened micropores and defect mesopores (≈4 nm) in the nanopetals, large interpetal pore space (≈39 nm), high surface area (388 m 2 g −1 ), as well as an ultrahigh loading metal atoms (27.3 wt%). Subsequently, a superior peroxidases-like activity (36.6-fold increment in the turnover frequency) facilitates significantly strengthened ROS generation and damage of biomolecules. Moreover, the employment of apoferritin modification/loading leads to particle dispersion in solution and concomitant drug loading. The following cancer cell re-sensitization is proven to be advantageous for boosting ROS-facilitated treatment of drug-resistant tumors, opening up new avenues for ROS therapy.
Carbon materials, including carbon fibers, graphite, diamond, carbon foams, carbon nanotubes, and graphene, are attractive reinforcements for aluminum matrix composites due to their excellent mechanical and/or physical properties as well as light weight. Carbon materials reinforced aluminum (C/Al) composites are promising materials in many areas such as aerospace, thermal management, and automobile. However, there are still some challenging problems that need to be resolved, such as interfacial reactions, low wettability, and anisotropic properties. These problems have limited the use of these composites. This review mainly focuses on the categories, fabrication processes, existing problems and solutions, coatings and interfaces, challenges and opportunities of C/Al composites so as to provide a useful reference for future research.
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