Robust and Tumor-Environment-Activated DNA Cross-Linker Driving Nanoparticle Accumulation for Enhanced Therapeutics  

作　　者：Zhicong Chao Hongwei Lu Fan Xiao Chen Shao Zixiang Wei Jiantao Yu Xindan Zhang Li Lin Leilei Tian 

机构地区：[1]Department of Materials Science and Engineering,Southern University of Science and Technology,Shenzhen,Guangdong 518055(China)

出　　处：《CCS Chemistry》2020年第5期349-361,共13页中国化学会会刊（英文）

基　　金：support by grants from the National Natural Science Foundation of China(no.51973089);Shenzhen Fundamental Research Programs(nos.JCYJ20160226193029593 and JCYJ20170817105645935);Shenzhen Science and Technology Innovation Commission(grant no.KQTD20170810111314625);Guangdong Innovative and Entrepreneurial Research Team Program(no.2016ZT06G587).

摘　　要：Agglomeration of therapeutic nanoparticles in response to tumor microenvironments is a promising approach to enhance drug accumulation and improve therapeutic efficacy.Cytosine-rich DNA sequences show potential as ideal cross-linkers to drive nanoparticle agglomeration because they can sensitively respond to weak acidity and form interchain folding.However,the in vivo application of DNA is generally limited by its poor biostability;as a consequence,modifications with unprotected DNA cross-linkers can enhance the accumulation of nanoparticles twofold at the tumor site.Facing this challenge,we have designed and developed a protection and tumor-environment activation strategy to enable the in vivo application of a DNA cross-linker.Specifically,reactive oxygen species(ROS)-responsive polyethylene glycol(PEG)was modified on the nanoparticle surface together with the DNA crosslinker,which protects DNA from degradation during the blood circulation;meanwhile,when arriving at the tumor site,the nanoparticles shed the PEG shell as a response to ROS to uncover and activate the DNA cross-linkers.Using this strategy,a sevenfold enhancement in tumor accumulation was achieved owing to both superior pH sensitivity and improved stability of DNA cross-linkers.Finally,significantly improved therapeutic efficacy in in vivo anticancer treatment was realized by using this agglomeration strategy driven by protected and stimuli-activated DNA cross-linkers.

关 键 词：pH-responsive DNA ROS-responsive PEG tumor retention nanoparticles for multimodal therapy in vivo tumor treatment 

分 类 号：R730.5[医药卫生—肿瘤]