Biodegradable nanoparticle-enhanced chemoimmunotherapy based on precise tumor killing and tumor microenvironment regulation strategy†

IF 2.5 3区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY

New Journal of Chemistry Pub Date : 2025-03-10 DOI:10.1039/D4NJ04942J

Meng-Jiao Gao, Ran Wei, Chen-Chen Li, Li Wang, Can Liu, Xu-Ying Liu, Shu-Yan Liu and Yan-Fei Kang

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Abstract

Although chemotherapy-based immunotherapy has promoted tumor therapeutic effects, it is counteracted by the negative immune regulation of the tumor microenvironment (TME). Herein, pH-responsive SN-38/CXB@mPEG-PAE nanocomplexes were fabricated to improve the immunosuppressive tumor microenvironment (ITM), thereby enhancing antitumor activity. In the acidic TME, chemotherapeutic drug 7-ethyl-10-hydroxycamptothecin (SN-38) and celecoxib (CXB, an inhibitor of cyclooxygenase-2) were released, indicating that these nanocomplexes precisely targeted tumor cells. Moreover, the released SN-38, in addition to directly eliminating cancer cells by inducing tumor cell apoptosis and cell cycle arrest, induced immunogenic cell death (ICD) in vitro. The released CXB could further activate dendritic cells (DCs) by inhibiting the COX-2/PGE₂ axis, which synergistically activated the immune system to promote treatment efficacy. This study provides a novel functional nanoplatform to improve the ITM for enhanced chemotherapy-based immunotherapy.

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基于精确肿瘤杀伤和肿瘤微环境调控策略的可生物降解纳米颗粒增强化学免疫疗法

以化疗为基础的免疫治疗虽然促进了肿瘤的治疗效果，但却被肿瘤微环境（tumor microenvironment， TME）的负性免疫调节所抵消。本文制备了ph响应型SN-38/CXB@mPEG-PAE纳米复合物，以改善免疫抑制肿瘤微环境（ITM），从而增强抗肿瘤活性。在酸性TME中，化疗药物7-乙基-10-羟基喜树碱（SN-38）和塞来昔布（CXB，一种环氧化酶-2抑制剂）被释放，表明这些纳米复合物精确靶向肿瘤细胞。此外，释放的SN-38除了通过诱导肿瘤细胞凋亡和细胞周期阻滞直接消灭癌细胞外，还在体外诱导免疫原性细胞死亡（ICD）。释放的CXB可通过抑制COX-2/PGE2轴进一步激活树突状细胞（dc），协同激活免疫系统，促进治疗效果。本研究提供了一种新的功能纳米平台来改进ITM，以增强基于化疗的免疫治疗。

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