Penetrable Nanoplatform for "Cold" Tumor Immune Microenvironment Reeducation.
Penetrable Nanoplatform for "Cold" Tumor Immune Microenvironment Reeducation.
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用于“冷”肿瘤免疫微环境再教育的可穿透纳米平台
DOI：
10.1002/advs.202000411
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Jiang C
中科院分区：
文献类型：
--
作者：
Chen Q;He Y;Wang Y;Li C;Zhang Y;Guo Q;Zhang Y;Chu Y;Liu P;Chen H;Zhou Z;Zhou W;Zhao Z;Li X;Sun T;Jiang C
缺乏肿瘤浸润淋巴细胞（TIL）和肿瘤环境中过表达的免疫抑制细胞（主要是髓源性抑制细胞（MDSC））的抗性是阻碍免疫疗法对“免疫冷”肿瘤的有效性的两个主要挑战。此外，实体癌中存在的天然物理屏障也限制了药物的更深递送。在这里，开发了一种肿瘤靶向和光响应可穿透的纳米平台（Apt/PDGs^s@pMOF），以引起细胞毒性T细胞（CTL）的肿瘤内浸润并同时再教育免疫抑制微环境。特别地，基于卟啉金属有机框架（pMOF）的光动力疗法（PDT）诱导肿瘤免疫原性细胞死亡（ICD）以促进CTL肿瘤内浸润和热“免疫-冷”肿瘤。在被PDT触发后，近10 nm吸附的载药树枝状聚合物从纳米平台上脱落并扩散到更深的肿瘤中，消除MDSC并逆转免疫抑制，最终增强免疫反应。同时，所设计的纳米平台还具有全身MDSC抑制作用，并适度改善整体抗肿瘤免疫应答，从而在不太显著的免疫相关不良反应（irAE）诱导下有效抑制远端肿瘤。开发可穿透的纳米平台以引起细胞毒性T细胞（CTL）的肿瘤内浸润并同时再教育免疫抑制微环境。特别是，由光动力疗法（PDT）诱导的免疫原性细胞死亡促进CTL浸润，在被PDT触发后，载药树枝状聚合物扩散到更深的肿瘤中，消除髓源性抑制细胞并逆转免疫抑制，最终增强免疫应答。
Lack of tumor‐infiltration lymphocytes (TILs) and resistances by overexpressed immunosuppressive cells (principally, myeloid‐derived suppressor cells (MDSCs)) in tumor milieu are two major challenges hindering the effectiveness of immunotherapy for “immune‐cold” tumors. In addition, the natural physical barrier existing in solid cancer also limits deeper delivery of drugs. Here, a tumor‐targeting and light‐responsive‐penetrable nanoplatform (Apt/PDGs^s@pMOF) is developed to elicit intratumoral infiltration of cytotoxic T cells (CTLs) and reeducate immunosuppressive microenvironment simultaneously. In particular, porphyrinic metal–organic framework (pMOF)–based photodynamic therapy (PDT) induces tumor immunogenic cell death (ICD) to promote CTLs intratumoral infiltration and hot “immune‐cold” tumor. Upon being triggered by PDT, the nearly 10 nm adsorbed drug‐loaded dendrimer de‐shields from the nanoplatform and spreads into the deeper tumor, eliminating MDSCs and reversing immunosuppression, eventually reinforcing immune response. Meanwhile, the designed nanoplatform also has a systemic MDSC inhibition effect and moderate improvement of overall antitumor immune responses, resulting in effective suppression of distal tumors within less significant immune‐related adverse effects (irAEs) induced. A penetrable nanoplatform is developed to elicit intratumoral infiltration of cytotoxic T cells (CTLs) and reeducate immunosuppressive microenvironment simultaneously. In particular, immunogenic cell death induced by photodynamic therapy (PDT) promotes CTLs infiltration, upon being triggered by PDT, drug‐loaded dendrimer spreads into deeper tumor, eliminating myeloid‐derived suppressor cells and reversing immunosuppression, eventually reinforcing immune responses.
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DOI：
10.3322/caac.20114
发表时间：
2011-07
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Agostinis P;Berg K;Cengel KA;Foster TH;Girotti AW;Gollnick SO;Hahn SM;Hamblin MR;Juzeniene A;Kessel D;Korbelik M;Moan J;Mroz P;Nowis D;Piette J;Wilson BC;Golab J
通讯作者：
Golab J
通过逐层组装构建的基于介孔二氧化硅的多功能治疗诊断纳米平台，可实现出色的光动力/化疗治疗
影响因子：
14
作者：
Chen, Wei-Hai;Luo, Guo-Feng;Zhang, Xian-Zheng
通讯作者：
Zhang, Xian-Zheng
影响因子：
5
作者：
Cheng, Alan K. H.;Sen, Dipankar;Yu, Hua-Zhong
通讯作者：
Yu, Hua-Zhong
DOI：
10.1097/ppo.0000000000000006
发表时间：
2013-11
期刊：
Cancer journal (Sudbury, Mass.)
影响因子：
--
作者：
Albeituni SH;Ding C;Yan J
通讯作者：
Yan J
影响因子：
5.8
作者：
BOUFFARD, DY;LALIBERTE, J;MOMPARLER, RL
通讯作者：
MOMPARLER, RL