Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum-DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.
Convenient and fast testing using an immunochromatography test strip (ICTS) enables rapid yes/no decisions regarding a disease to be made. However, the fundamental limitations of an ICTS, such as a lack of quantitative and sensitive analysis, severely hampers its application in reliable medical testing for the early detection of cancer. Herein, we overcame these limitations by integrating an ICTS with quantum dot nanobeads (QD nanobeads), which were fabricated by encapsulating QDs within modified poly(tert-butyl acrylate-co-ethyl acrylate-co-methacrylic acid) and served as a robust signal-generating reagent for the ICTS. Prostate specific antigen (PSA) was used as a model analyte to demonstrate the performance of the QD nanobeads-based ICTS platform. Under optimized conditions, the concentration of PSA could be determined within 15 min with high sensitivity and specificity using only 40 μL of sample. The detection limit was enhanced by ∼12-fold compared with that of an ICTS that used QDs encapsulated by commercial 11mercaptoundecanoic acid (QDs@MUA) as the signal-generating reagent. At the same time, the possible clinical utility of this approach was demonstrated by measurements recorded from PSA-positive patient specimens. Our data suggest that the QD nanobeads-based ICTS platform is not only rapid and low-cost but also highly sensitive and specific for use in quantitative pointof-care diagnostics; thus, it holds promise for becoming a part of routine medical testing for the early cancer of detection.
Nonaqueous redox
flow batteries (RFBs) are a promising energy storage technology that
enables increased cell voltage and high energy capacity compared to
aqueous RFBs. Herein, we first report a novel approach to substantially
increase the energy density based on the miscible liquid redox materials
2,5-di-tert-butyl-1-methoxy-4-[2′-methoxyethoxy]benzene
catholyte and 2-methylbenzophenone anolyte. This system has a high
theoretical cell voltage of 2.97 V and a calculated energy density
of 223 Wh L–1 that is much higher than those of
previously reported nonaqueous organic RFBs. Our reported redox flow
chemistry displays excellent electrochemical performance and stability
under cyclic voltammetry, bulk electrolysis, and flow cell conditions.
A proof-of-principle RFB delivers a coulombic efficiency of 95% and
energy efficiency of 70% and represents significant progress toward
high energy density RFBs.
Enhanced tumor cellular internalization and triggered drug release are two main concerns in the development of nanoparticles for antitumor drug delivery. In this article, a new kind of smart pH- and reduction-dual-responsive drug- loaded PEG coated polymeric lipid vesicle (PPLV) that can achieve both enhanced tumor cellular internalization and triggered drug release has been designed and prepared. The PPLVs were formed from amphiphilic dextran derivatives. The antitumor drug, doxorubicin (DOX), was loaded in the cores of the PPLVs. The newly developed PPLVs had a nanosized structure (∼40 nm) with PEG coating, so they were neutral and had high colloidal stability in the blood circulation. The in vitro physicochemical characterizations showed that the PPLVs lose their PEG coating and expose the positive surface charge under acidic environments. The in vitro cellular uptake study indicated that the acidic-treated PPLVs can efficiently enter tumor cells. It has been demonstrated by in vitro DOX release profiles that the PPLVs can achieve a triggered drug release in response to the reduction environment. The MTT assay demonstrated that DOX-loaded PPLVs treated with pH 5.0 solution had higher antitumor activity than DOX-loaded PPLVs treated with pH 7.4 solution. These results suggested that the PPLVs were promising nanoparticles for smart antitumor drug delivery applications.
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