文献类型：期刊文献

英文题名：Size-transformable nanoparticles with sequentially triggered drug release and enhanced penetration for anticancer therapy

作者：Li, Yulin[1,5];Wang, Liudi[1];Zhong, Guoqiang[1];Wang, Guoying[1];Zhu, Yanzhao[4];Li, Jian[2];Xiao, Lan[6];Chu, Yanhui[4];Wu, Yan[4];Li, Kaichun[2];Gao, Jie[3]

机构：[1]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Sch Mat Sci & Engn, Minist Educ,Key Lab Ultrafine Mat,Engn Res Ctr Bio, Shanghai 200237, Peoples R China;[2]Tongji Univ, Dept Oncol, Sch Med, Shanghai Peoples Hosp 4, Shanghai 200434, Peoples R China;[3]Naval Med Univ, Shanghai Changhai Hosp, Changhai Clin Res Unit, Shanghai 200433, Peoples R China;[4]Mudanjiang Med Univ, Coll Life Sci, Mudanjiang 157011, Peoples R China;[5]Shanghai Univ, Wenzhou Inst, Wenzhou 325000, Peoples R China;[6]Queensland Univ Technol, Ctr Biomed Technol, Brisbane, Qld 4059, Australia

年份：2023

卷号：16

期号：8

起止页码：11186

外文期刊名：NANO RESEARCH

收录：;EI(收录号：20233014445706);WOS:【SCI-EXPANDED(收录号:WOS:001036824400003)】；

基金：This research was supported by the National Basic Research Program of China (973 Program, No. 2012CB933600), the National Natural Science Foundation of China (Nos. 81771964 and 82072051) and the Shanghai Municipal Natural Science Foundation (No. 15ZR1408500). This work was funded by the Special Project of Clinical Research of Health Industry of Shanghai Municipal Health Commission (No. 201940178), the Scientific Research Project of Hongkou District Health Committee of Shanghai (No. 2002-17), the Clinical Research Project of Wu Jieping Medical Foundation (No. 320.6750.2020-18-2), and the Research Project of Shanghai Fourth People's Hospital (No. sykyqd 00701 & 00702).

语种：英文

外文关键词：sequentially triggered drug release; size-transformable; nanoparticles; tumor penetration; anticancer therapy; drug delivery

摘要：There are several limitations to the application of nanoparticles in the treatment of cancer, including their low drug loading, poor colloidal stability, insufficient tumor penetration, and uncontrolled release of the drug. Herein, gelatin/laponite (LP)/doxorubicin (GLD) nanoparticles are developed by crosslinking LP with gelatin for doxorubicin delivery. GLD shows high doxorubicin encapsulation efficacy (99%) and strong colloidal stability, as seen from the unchanged size over the past 21 days and reduced protein absorption by 48-fold compared with unmodified laponite/doxorubicin nanoparticles. When gelatin from 115 nm GLD reaches the tumor site, matrix metallopeptidase-2 (MMP-2) from the tumor environment breaks it down to release smaller 40 nm LP nanoparticles for effective tumor cell endocytosis. As demonstrated by superior penetration in both in vitro three-dimensional (3D) tumor spheroids (138-fold increase compared to the free drug) and in vivo tumor models. The intracellular low pH and MMP- 2 further cause doxorubicin release after endocytosis by tumor cells, leading to a higher inhibitory potential against cancer cells. The improved anticancer effectiveness and strong in vivo biocompatibility of GLD have been confirmed using a mouse tumor-bearing model. MMP-2/pH sequentially triggered anticancer drug delivery is made possible by the logical design of tumor-penetrating GLD, offering a useful method for anticancer therapy.