Acid-Activatable Versatile Micelleplexes for PD-L1 Blockade Enhanced Cancer Photodynamic Immunotherapy

doi:10.1021/acs.nanolett.6b01994

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	Acid-Activatable Versatile Micelleplexes for PD-L1 Blockade Enhanced Cancer Photodynamic Immunotherapy
	Wang, Dangge 2,3,4; Wang, Tingting 2,3,4; Liu, Jianping 2,3; Yu, Haijun2,3 ; Jiao, Shi 1; Feng, Bing 2,3,4; Zhou, Fangyuan 2,3; Fu, Yuanlei 2,3; Yin, Qi2,3 ; Zhang, Pengcheng2,3
刊名	NANO LETTERS
	2016-09
卷号	16 期号:9 页码:5503-5513
关键词	Micelleplexes acid-activatable photodynamic therapy cancer immunotherapy RNA interference
ISSN号	1530-6984
DOI	10.1021/acs.nanolett.6b01994
文献子类	Article
英文摘要	Photodynamic therapy (PDT) has emerged as a promising clinical modality for cancer therapy due to its ability to initiate an antitumor immune response. However, PDT-mediated cancer immunotherapy is severely impaired by tumor-cell immunosuppression of host T cell antitumor activity through the programmed cell death 1 ligand (PD-L1) and programmed cell death receptor 1 (PD-1) (PD-L1PD-1) immune checkpoint pathway. Here, we demonstrate that PDT-mediated cancer immunotherapy can be augmented by PD-L1 knockdown (KD) in tumor cells. We rationally designed a versatile micelleplex by integrating an acid-activatable cationic micelle, photosensitizer (PS), and small interfering RNA (siRNA). The micelleplex was inert at physiological pH conditions and activated only upon internalization in the acidic endocytic vesicles of tumor cells for fluorescence imaging and PDT. Compared to PDT alone, the combination of PDT and PD-L1 KD showed significantly enhanced efficacy for inhibiting tumor growth and distant metastasis in a B16-F10 melanoma xenograft tumor model. These results suggest that acid-activatable micelleplexes utilizing PDT-induced cancer immunotherapy are more effective when combined with siRNA-mediated PD-L1 blockade. This study could provide a general strategy for enhancing the therapy efficacy of photodynamic cancer therapy.
资助项目	National Basic Research Program of China[2013CB932704] ; National Natural Science Foundation of China[81373359] ; National Natural Science Foundation of China[31671024] ; National Natural Science Foundation of China[31622025] ; National Natural Science Foundation of China[81521005] ; Youth Innovation Promotion Association CAS[2014248]
WOS关键词	HEAT-SHOCK PROTEINS ; FACTOR-KAPPA-B ; BREAST-CANCER ; ANTITUMOR IMMUNITY ; GENE DELIVERY ; THERAPY ; TUMORS ; CELLS ; COMBINATION ; NANOPARTICLES
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000383412100029
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275913]
专题	药物制剂研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Yu, Haijun; Li, Yaping
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China; 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China;
推荐引用方式 GB/T 7714	Wang, Dangge,Wang, Tingting,Liu, Jianping,et al. Acid-Activatable Versatile Micelleplexes for PD-L1 Blockade Enhanced Cancer Photodynamic Immunotherapy[J]. NANO LETTERS,2016,16(9):5503-5513.
APA	Wang, Dangge.,Wang, Tingting.,Liu, Jianping.,Yu, Haijun.,Jiao, Shi.,...&Li, Yaping.(2016).Acid-Activatable Versatile Micelleplexes for PD-L1 Blockade Enhanced Cancer Photodynamic Immunotherapy.NANO LETTERS,16(9),5503-5513.
MLA	Wang, Dangge,et al."Acid-Activatable Versatile Micelleplexes for PD-L1 Blockade Enhanced Cancer Photodynamic Immunotherapy".NANO LETTERS 16.9(2016):5503-5513.