Sequential acid/reduction response of triblock copolymeric nanomicelles to release camptothecin and toll-like receptor 7/8 agonist for orchestrated chemoimmunotherapy.
Sequential acid/reduction response of triblock copolymeric nanomicelles to release camptothecin and toll-like receptor 7/8 agonist for orchestrated chemoimmunotherapy.
复制标题
三嵌段共聚纳米胶束的顺序酸/还原反应释放喜树碱和toll样受体7/8激动剂，用于精心安排的化学免疫治疗。
DOI：
10.1186/s12951-022-01577-5
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发表时间：
2022-08-11
影响因子：
10.2
通讯作者：
Zhang, Zhiyue
中科院分区：
文献类型：
--
作者：
Ge, Xiaoyan;Hao, Yanyun;Li, Hui;Zhao, Huajun;Liu, Yang;Liu, Yutong;Li, Xia;Chen, Hongfei;Zou, Jing;Zhang, Shiying;Huang, Lingling;Shan, Gang;Zhang, Zhiyue
关键词：
Immunosuppressive tumor immune microenvironment (TIME) lowers immunotherapy effectiveness. Additionally, low penetration efficiency and unpredictable drug release in tumor areas restrict tumor therapy. A triblock copolymeric micelle (NanoPCPT+PIMDQ) was developed to carry the chemotherapeutic drug camptothecin (CPT) and the TLR7/8 agonist 1-(4-(aminomethyl)benzyl)-2-butyl-1H-imidazo[4,5-c] quinoline-4-amine (IMDQ) to achieve deep tumor penetration and on-demand drug release by responding to acid and reduction stimuli sequentially. The synergistic antitumour efficacy of NanoPCPT+PIMDQ was assessed both in vitro and in vivo. NanoPCPT+PIMDQ is composed of a hydrophilic PEG(polyethylene glycol) outer layer, an acid-sensitive EPEMA middle layer, and a drug inner core. Upon intratumoral injection, (i) NanoPCPT+PIMDQ first responds to the acidic tumor microenvironment and disintegrates to PIMDQ and PCPT, penetrating deep regions of the tumor; (ii) tumor cells are killed by the released CPT; (iii) DCs are activated by PIMDQ to increase the infiltration of cytotoxic T lymphocyte (CTL); and (iv) both downregulated Foxp3+ Tregs by CPT and repolarized M2 macrophages by PIMDQ can relieve the TIME. This pH/GSH-responsive triblock polymer-drug conjugate reduces immunosuppression and enhances the infiltration of CTLs by codelivering CPT and IMDQ in a controllable manner, providing a promising platform for synergistic tumor chemoimmunotherapy. The online version contains supplementary material available at 10.1186/s12951-022-01577-5.
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DOI：
10.1038/s41578-021-00372-2
发表时间：
2022
期刊：
Nature reviews. Materials
影响因子：
--
作者：
Roth GA;Picece VCTM;Ou BS;Luo W;Pulendran B;Appel EA
通讯作者：
Appel EA
表观遗传调控与基因治疗介导的免疫检查点阻断相结合可诱导体内抗肿瘤作用和免疫反应
影响因子：
16.6
作者：
Fang H;Guo Z;Chen J;Lin L;Hu Y;Li Y;Tian H;Chen X
通讯作者：
Chen X
影响因子：
10.8
作者：
Li, Zimu;Yang, Yao;Zeng, Xiaowei
通讯作者：
Zeng, Xiaowei
影响因子：
28.1
作者：
Kulkarni, Ashish;Chandrasekar, Vineethkrishna;Sengupta, Shiladitya
通讯作者：
Sengupta, Shiladitya
影响因子：
10.9
作者：
Buchwald ZS;Nasti TH;Lee J;Eberhardt CS;Wieland A;Im SJ;Lawson D;Curran W;Ahmed R;Khan MK
通讯作者：
Khan MK