关键词： CTGF, connective tissue growth factor CaO2 Chemotherapy DOX, doxorubicin DSPE-PEG2000, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] ECM, extracellular matrix EPR, enhanced permeability and retention FBS, fetal bovine serum HA, hyaluronic acid HAase, hyaluronidase HIF-1 HIF-1α, hypoxia-inducible factor 1α Hypoxia MCTS, multicellular tumor spheroids MS, monostearin MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MnO2 NP, nanoparticle Nanoparticle OA, oleic acid P-gp, P-glycoprotein PDT, photodynamic therapy TEM, transmission electron microscopy TME, tumor microenvironment Transportation Tumor CTGF, connective tissue growth factor CaO2 Chemotherapy DOX, doxorubicin DSPE-PEG2000, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] ECM, extracellular matrix EPR, enhanced permeability and retention FBS, fetal bovine serum HA, hyaluronic acid HAase, hyaluronidase HIF-1 HIF-1α, hypoxia-inducible factor 1α Hypoxia MCTS, multicellular tumor spheroids MS, monostearin MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MnO2 NP, nanoparticle Nanoparticle OA, oleic acid P-gp, P-glycoprotein PDT, photodynamic therapy TEM, transmission electron microscopy TME, tumor microenvironment Transportation Tumor

来  源：   DOI：10.1016/j.apsb.2021.04.021   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.
摘要：
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