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	Sequentially responsive therapeutic peptide assembling nanoparticles for dual-targeted cancer immunotherapy
	Cheng, Keman1,2; Ding, Yanping2,3; Zhao, Ying2,3; Ye, Shefang1; Zhao, Xiao2; Zhang, Yinlong2; Ji, Tianjiao2; Wu, Huanhuan1; Wang, Bin2,3; Anderson, Gregory J.4
刊名	Nano letters
	2018-05-01
卷号	18期号:5页码:3250-3258
关键词	Peptide self-assembly Dual-responsive Dual-targeted Controllable drug release Cancer immunotherapy
ISSN号	1530-6984
DOI	10.1021/acs.nanolett.8b01071
通讯作者	Ding, yanping(dingyp@nanoctr.cn) ; Ren, lei(renlei@xmu.edu.cn) ; Nie, guangjun(niegj@nanoctr.cn)
英文摘要	Combination therapeutic regimen is becoming a primary direction for current cancer immunotherapy to broad the antitumor response. functional nanomaterials offer great potential for steady codelivery of various drugs, especially small molecules, therapeutic peptides, and nucleic acids, thereby realizing controllable drug release, increase of drug bioavailability, and reduction of adverse effects. herein, a therapeutic peptide assembling nanoparticle that can sequentially respond to dual stimuli in the tumor extracellular matrix was designed for tumor-targeted delivery and on-demand release of a short d-peptide antagonist of programmed cell death-ligand 1 ((d)ppa-1) and an inhibitor of idoleamine 2,3-dioxygenase (nlg919). by concurrent blockade of immune checkpoints and tryptophan metabolism, the nanoformulation increased the level of tumor-infiltrated cytotoxic t cells and in turn effectively inhibited melanoma growth. to achieve this, an amphiphilic peptide, consisting of a functional 3-diethylaminopropyl isothiocyanate (deap) molecule, a peptide substrate of matrix metalloproteinase-2 (mmp-2), and (d)ppa-1, was synthesized and coassembled with nlg919. the nanostructure swelled when it encountered the weakly acidic tumor niche where deap molecules were protonated, and further collapsed due to the cleavage of the peptide substrate by mmp-2 that is highly expressed in tumor stroma. the localized release of (d)ppa-1 and nlg919 created an environment which favored the survival and activation of cytotoxic t lymphocytes, leading to the slowdown of melanoma growth and increase of overall survival. together, this study offers new opportunities for dual-targeted cancer immunotherapy through functional peptide assembling nanoparticles with design features that are sequentially responsive to the multiple hallmarks of the tumor microenvironment.
WOS关键词	ANTITUMOR IMMUNE-RESPONSES ; T-CELL EXHAUSTION ; DELIVERY ; ANTIBODY ; PATHWAY ; INHIBITION ; RESISTANCE ; DISCOVERY ; BLOCKADE ; EVASION
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
WOS类目	Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000432093200072
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2177614
专题	高能物理研究所
通讯作者	Ding, Yanping; Ren, Lei; Nie, Guangjun
作者单位	1.Xiamen Univ, Coll Mat, Key Lab Biomed Engn Fujian Prov, Dept Biomat, Xiamen 361005, Peoples R China 2.Natl Ctr Nanosci & Technol NCNST, CAS Ctr Excellence Nanosci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, 11 Beiyitiao, Beijing 100190, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Royal Brisbane Hosp, QIMR Berghofer Med Res Inst, Iron Metab Lab, Locked Bag 2000, Brisbane, Qld 4029, Australia
推荐引用方式 GB/T 7714	Cheng, Keman,Ding, Yanping,Zhao, Ying,et al. Sequentially responsive therapeutic peptide assembling nanoparticles for dual-targeted cancer immunotherapy[J]. Nano letters,2018,18(5):3250-3258.
APA	Cheng, Keman.,Ding, Yanping.,Zhao, Ying.,Ye, Shefang.,Zhao, Xiao.,...&Nie, Guangjun.(2018).Sequentially responsive therapeutic peptide assembling nanoparticles for dual-targeted cancer immunotherapy.Nano letters,18(5),3250-3258.
MLA	Cheng, Keman,et al."Sequentially responsive therapeutic peptide assembling nanoparticles for dual-targeted cancer immunotherapy".Nano letters 18.5(2018):3250-3258.

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