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

• DOI: 10.1016/j.apsb.2021.04.021
• Publication Date: 2021-05-07T16:49:08Z
• Authors: 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
• Keywords: Nanocarriers; Efflux; Penetration (warfare)

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