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一种可注射的复合水凝胶,包含聚多巴胺包覆的姜黄素纳米粒子和吲哚美辛,用于增强乳腺癌的联合化疗-光热-免疫治疗。

An injectable composite hydrogel containing polydopamine-coated curcumin nanoparticles and indoximod for the enhanced combinational chemo-photothermal-immunotherapy of breast tumors.

机构信息

College of Pharmacy, Southwest Minzu University, Chengdu 610041, China.

College of Pharmacy, Southwest Minzu University, Chengdu 610041, China; Institute of Qinghai-Tibetan Plateau, Southwest Minzu University, Chengdu 610041, China.

出版信息

Colloids Surf B Biointerfaces. 2024 Dec;244:114130. doi: 10.1016/j.colsurfb.2024.114130. Epub 2024 Jul 28.


DOI:10.1016/j.colsurfb.2024.114130
PMID:39121570
Abstract

The complexity and compensatory evolution of tumors weaken the effectiveness of single antitumor therapies. Therefore, multimodal combination therapies hold great promise in defeating tumors. Herein, we constructed a multi-level regulatory co-delivery system based on chemotherapy, phototherapy, and immunotherapy. Briefly, curcumin (Cur) was prepared as nanoparticles and coated with polydopamine (PDA) to form PCur-NPs, which along with an immune checkpoint inhibitor (indoximod, IND) were then loaded into a thermosensitive Pluronic F127 (F127) hydrogel to form a multifunctional nanocomposite hydrogel (PCur/IND@Gel). The in situ-formed hydrogel exhibited excellent photothermal conversion efficiency and sustained drug release behavior both in vitro and in vivo. In addition, PCur-NPs showed enhanced cellular uptake and cytotoxicity under NIR laser irradiation and induced potent immunogenic cell death (ICD). After intratumoral injection of PCur/IND@Gel, significant apoptosis in 4T1 tumors was induced, dendritic cells in lymph nodes were highly activated, potent CD8 and CD4 antitumor immune responses were elicited and regulative T cells in tumors were significantly reduced, which notably inhibited the tumor growth and prolonged the survive time of 4T1 tumor-bearing mice. Therefore, this injectable nanocomposite hydrogel is a promising drug co-delivery platform for chemo-photothermal-immunotherapy of breast tumors.

摘要

肿瘤的复杂性和代偿进化削弱了单一抗肿瘤疗法的效果。因此,多模式联合治疗在战胜肿瘤方面具有巨大的潜力。在此,我们构建了一种基于化学疗法、光疗和免疫疗法的多层次调控共递药系统。简而言之,将姜黄素(Cur)制备成纳米颗粒并用聚多巴胺(PDA)进行包覆,形成 PCur-NPs,随后将免疫检查点抑制剂(indoximod,IND)载入热敏性 Pluronic F127(F127)水凝胶中,形成多功能纳米复合水凝胶(PCur/IND@Gel)。原位形成的水凝胶在体外和体内均表现出优异的光热转换效率和持续的药物释放行为。此外,PCur-NPs 在近红外激光照射下表现出增强的细胞摄取和细胞毒性,并诱导强烈的免疫原性细胞死亡(ICD)。在肿瘤内注射 PCur/IND@Gel 后,4T1 肿瘤中诱导了明显的细胞凋亡,淋巴结中的树突状细胞被高度激活,产生了强大的 CD8 和 CD4 抗肿瘤免疫反应,并且肿瘤中的调节性 T 细胞明显减少,显著抑制了肿瘤生长并延长了荷瘤 4T1 小鼠的存活时间。因此,这种可注射纳米复合水凝胶是一种有前途的用于乳腺癌化疗-光疗-免疫治疗的药物共递药平台。

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