Size-transformable nanoparticles with sequentially triggered drug release and enhanced penetration for anticancer therapy  

作　　者：Yulin Li Liudi Wang Guoqiang Zhong Guoying Wang Yanzhao Zhu Jian Li Lan Xiao Yanhui Chu Yan Wu Kaichun Li Jie Gao 

机构地区：[1]Engineering Research Centre for Biomedical Materials of Ministry of Education,The Key Laboratory for Ultrafine Materials of Ministry of Education,Frontiers Science Center for Materiobiology and Dynamic Chemistry,School of Material Science and Engineering,East China University of Science and Technology,Shanghai 200237,China [2]Department of Oncology Shanghai Fourth People’s Hospital,School of Medicine,Tongji University,Shanghai 200434,China [3]Changhai Clinical Research Unit,Shanghai Changhai Hospital,Naval Medical University,Shanghai 200433,China [4]College of Life Sciences Mudanjiang Medical University,Mudanjiang 157011,China [5]Wenzhou Institute of Shanghai University,Wenzhou 325000,China [6]Centre for Biomedical Technologies,Queensland University of Technology,Brisbane,QLD 4059,Australia

出　　处：《Nano Research》2023年第8期11186-11196,共11页纳米研究（英文版）

基　　金：supported by the National Basic Research Program of China(973 Program,No.2012CB933600);the National Natural Science Foundation of China(Nos.81771964 and 82072051);the Shanghai Municipal Natural Science Foundation(No.15ZR1408500);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);the Research Project of Shanghai Fourth People’s Hospital(No.sykyqd 00701&00702).

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.

关 键 词：sequentially triggered drug release size-transformable NANOPARTICLES tumor penetration anticancer therapy drug delivery 

分 类 号：R730.5[医药卫生—肿瘤] TB383[医药卫生—临床医学]