A smart O2-generating nanocarrier optimizes drug transportation comprehensively for chemotherapy improving

• 作者: Xiaojuan Zhang Chuanchuan He Yun Sun Xiaoguang Liu Yan Chen Chen Chen Ruicong Yan Ting Fan Tan Yang Yao Lu Jun Luo Xiang Ma Guangya Xiang
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（11）
• 所属期刊栏目: Origimal articles
• 页码范围: 3608-3621
• 页数: 14页
• 语种: 英文

摘要

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 enhance-ment.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 neigh-boring 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,prolong-ing 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.