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

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.

• 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
• Journal: Acta pharmaceutica Sinica. B (Acta Pharm Sin B) Vol. 11 Issue 11 Pg. 3608-3621 (Nov 2021) ISSN: 2211-3835 [Print] Netherlands
• PMID: 34900540 (Publication Type: Journal Article)
• Copyright: © 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.