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• W3193899347 abstract "Hypoxic tumor microenvironment (TME) promotes tumor metastasis and drug resistance, leading to low efficiency of cancer chemotherapy. The development of targeted agents or multi-target therapies regulating hypoxic microenvironment is an important approach to overcome drug resistance and metastasis.In this study, chitosan oligosaccharide (COS)-coated and sialic acid (SA) receptor-targeted nano-micelles were prepared using film dispersion method to co-deliver cisplatin (CDDP) and nitric oxide (NO) (denoted as CTP/CDDP). In addition, we explored the mechanisms by which NO reversed CDDP resistance as well as enhanced anti-metastatic efficacy in hypoxic cancer cells.Because of the different affinities of COS and SA to phenylboronic acid (PBA) under different pH regimes, CTP/CDDP micelles with intelligent targeting property increased cellular uptake of CDDP and enhanced cytotoxicity to tumors, but reduced systemic toxicity to normal organs or tissues. In addition, CTP/CDDP showed stimulus-responsive release in TME. In terms of anti-tumor mechanism, CTP/CDDP reduced CDDP efflux and inhibited epithelial-mesenchymal transition (EMT) process of tumor by down-regulating hypoxia-inducible factor-1α (HIF-1α), glutathione (GSH), multidrug resistance-associated protein 2 (MRP2) and matrix metalloproteinase 9 (MMP9) expression, thus reversing drug resistance and metastasis of hypoxic tumor cells.The designed micelles significantly enhanced anti-tumor effects both in vitro and in vivo. These results suggested that CTP/CDDP represented a promising strategy to treat resistance and metastatic tumors." @default.
• W3193899347 created "2021-08-30" @default.
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• W3193899347 date "2021-08-16" @default.
• W3193899347 modified "2023-10-15" @default.
• W3193899347 title "Nitric oxide-releasing micelles with intelligent targeting for enhanced anti-tumor effect of cisplatin in hypoxia" @default.
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• W3193899347 doi "https://doi.org/10.1186/s12951-021-00989-z" @default.
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