期刊
ACS NANO
卷 14, 期 1, 页码 620-631出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b07212
关键词
combination therapy; nanovesicle mediated immunogenic cell death; photodynamic therapy; tumor microenvironment modulation; melanoma cancer immunotherapy
类别
资金
- Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
- National Natural Science Foundation of China (NSFC) [81471689, 81771873, 91859207]
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [ZICEB000087] Funding Source: NIH RePORTER
Combination therapy that could better balance immune activation and suppressive signals holds great potential in cancer immunotherapy. Herein, we serendipitously found that the pH-responsive nanovesicles (pRNVs) self-assembled from block copolymer polyethylene glycol-b-cationic polypeptide can not only serve as a nanocarrier but also cause immunogenic cell death (ICD) through preapoptotic exposure of calreticulin. After coencapsulation of a photosensitizer, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) and an indoleamine 2,3-dioxygenase inhibitor, indoximod (IND), pRNVs/HPPH/IND at a single low dose elicited significant antitumor efficacy and abscopal effect following laser irradiation in a B16F10 melanoma tumor model. Treatment efficacy attributes to three key factors: (i) singlet oxygen generation by HPPH-mediated photodynamic therapy (PDT); (ii) increased dendritic cell (DC) recruitment and immune response provocation after ICD induced by pRNVs and PDT; and (iii) tumor microenvironment modulation by IND via enhancing P-S6K phosphorylation for CD8(+) T cell development. This study exploited the nanocarrier to induce ICD for the host's immunity activation. The all-in-one smart nanovesicles allow the design of multifunctional materials to strengthen cancer immunotherapy efficacy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据