Sequentially responsive therapeutic peptide assembling nanoparticles for dual-targeted cancer immunotherapy
文献类型：期刊论文
| 作者 | 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
 |
| 出版日期 | 2018-05-01 |
| 卷号 | 18期号:5页码:3250-3258 |
| ISSN号 | 1530-6984 |
| 关键词 | Peptide self-assembly Dual-responsive Dual-targeted Controllable drug release Cancer immunotherapy |
| 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 |
| URI标识 | http://www.irgrid.ac.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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