Engineering Stimuli-Activatable Boolean Logic Prodrug Nanoparticles for Combination Cancer Immunotherapy

doi:10.1002/adma.201907210

	Engineering Stimuli-Activatable Boolean Logic Prodrug Nanoparticles for Combination Cancer Immunotherapy
	Hou, Bo 1,2,3; Zhou, Lei 1,2; Wang, Hui 3; Saeed, Madiha 1,2; Wang, Dangge 1,2; Xu, Zhiai 4; Li, Yaping 1,2; Yu, Haijun 1,2
刊名	ADVANCED MATERIALS
	2020-02-12
页码	11
关键词	Boolean logic gates cancer immunotherapy prodrug nanoparticles stimuli activation tumor microenvironment
ISSN号	0935-9648
DOI	10.1002/adma.201907210
通讯作者	Yu, Haijun(hjyu@simm.ac.cn)
英文摘要	Prodrug nanoparticles that codeliver the immune modulators to the tumor site are highly recommendable for cancer immunotherapy yet remain challenging. However, effective stimuli-responsive strategies that exploit the endogenous hallmarks of the tumor have paved the way for cancer immunotherapy. For the first time, the development of the Boolean logic prodrug nanoparticles (BLPNs) for tumor-targeted codelivery of immune modulators (e.g., immune activator and immune inhibitor) and combination immunotherapy is reported herein. A library of stimuli-activatable BLPNs is fabricated yielding YES/AND logic outputs by adjusting the input combinations, including extracellular matrix metalloproteins 2/9 (MMP-2/9), intracellular acidity (pH = 5.0-6.0), and reduction (glutathione) in the tumor microenvironment. Tunable and selective control over BLPNs dissociation and prodrug activation is achieved by specifying the connectivity of orthogonal stimuli-labile spacers while exploiting the endogenous signals at the tumor sites. The tumor-specific distribution of the BLPNs and stimuli-activation of the immune modulators for highly efficient cancer immunotherapy are further demonstrated. The results reported in this study may open a new avenue for tumor-specific delivery of immune therapeutics and precise cancer immunotherapy.
资助项目	National Natural Science Foundation of China[31622025] ; National Natural Science Foundation of China[51873228] ; National Natural Science Foundation of China[31671024] ; National Natural Science Foundation of China[81521005] ; Youth Innovation Promotion Association of Chinese Academy of Sciences[2014218] ; CAS President's International Fellowship Initiative Program[2019PB0023] ; Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences[2019-027]
WOS关键词	T-CELLS ; MEMORY ; RESISTANCE ; THERAPY ; DESIGN
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000512716900001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281613]
专题	中国科学院上海药物研究所
通讯作者	Yu, Haijun
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, 501 Haike Rd, Shanghai 201203, Peoples R China 3.Inner Magnolia Univ, Coll Chem & Chem Engn, Hohhot 010021, Peoples R China 4.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China
推荐引用方式 GB/T 7714	Hou, Bo,Zhou, Lei,Wang, Hui,et al. Engineering Stimuli-Activatable Boolean Logic Prodrug Nanoparticles for Combination Cancer Immunotherapy[J]. ADVANCED MATERIALS,2020:11.
APA	Hou, Bo.,Zhou, Lei.,Wang, Hui.,Saeed, Madiha.,Wang, Dangge.,...&Yu, Haijun.(2020).Engineering Stimuli-Activatable Boolean Logic Prodrug Nanoparticles for Combination Cancer Immunotherapy.ADVANCED MATERIALS,11.
MLA	Hou, Bo,et al."Engineering Stimuli-Activatable Boolean Logic Prodrug Nanoparticles for Combination Cancer Immunotherapy".ADVANCED MATERIALS (2020):11.