光动力疗法
免疫疗法
癌症研究
内化
癌症免疫疗法
癌细胞
癌症
免疫检查点
化学
光敏剂
免疫系统
医学
细胞
免疫学
内科学
生物化学
有机化学
作者
Dangge Wang,Tingting Wang,Jianping Liu,Haijun Yu,Jianzhong Shi,Bing Feng,Fangyuan Zhou,Yuanlei Fu,Qi Yin,Pengcheng Zhang,Zhiwen Zhang,Zhaocai Zhou,Yaping Li
出处
期刊:Nano Letters
[American Chemical Society]
日期:2016-08-17
卷期号:16 (9): 5503-5513
被引量:363
标识
DOI:10.1021/acs.nanolett.6b01994
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-L1-PD-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.
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