一种三重免疫调节的槲皮素纳米平台，用于增强T细胞功能并重塑肿瘤微环境
A triple-immunomodulatory quercetin nanoplatform to reinforce T-cell function and remodel tumor microenvironment.
摘要(中文译文)
免疫检查点抑制剂（ICIs）常因肿瘤微环境（TME）中T细胞浸润不足而导致临床疗效有限。为应对这一挑战，我们利用中药活性成分槲皮素（quercetin）作为替代性免疫检查点抑制剂，并开发了一种透明质酸包覆的锰嵌入介孔二氧化硅纳米颗粒（HA-MSN(Mn)），用于TME触发的槲皮素（Que）与Mn共递送，以增强癌症免疫治疗。该纳米平台利用TME内pH/氧化还原双重响应性MnO键断裂，触发纳米颗粒结构解体及后续控释。通过体外和体内模型，我们证明该纳米平台通过三重免疫调节机制增强T细胞功能并逆转免疫抑制性TME。具体而言：（1）Que和Mn均可独立促进树突状细胞（DC）成熟，有助于T细胞活化；（2）Mn和Que可独立促进M1型巨噬细胞极化，从而通过分泌免疫细胞因子将T细胞募集至肿瘤；（3）负载Que的HA-MSN(Mn)下调肿瘤细胞表面PD-L1表达，克服免疫逃逸并增强T细胞细胞毒性。此外，该纳米平台表现出与免疫调节相关的抗肿瘤效应，同时增强对肿瘤生长的抑制，且脱靶毒性极小。重要的是，本研究为槲皮素的多重免疫调节作用提供了更深入的见解，为免疫治疗提供了一种有前景的纳米技术驱动策略。
Abstract
Immune checkpoint inhibitors (ICIs) often exhibit limited clinical efficacy due to insufficient infiltration of T cells in the tumor microenvironment (TME). To address this challenge, we utilized quercetin, an active ingredient of traditional Chinese medicine, as an alternative ICI, and developed a hyaluronic acid-coated manganese-embedded mesoporous silica nanoparticle (HA-MSN(Mn) for TME-triggered co-delivery quercetin (Que) and Mn to potentiate cancer immunotherapy. This nanoplatform exploits the dual pH/redox-responsive MnO bond cleavage within the TME, triggering structural disintegration of the nanoparticles and subsequent controlled release. Through in vitro and in vivo models, we demonstrated that this nanoplatform employs a triple immunomodulatory mechanism to enhance T-cell function and reverse the immunosuppressive TME. Specifically: (1) both Que and Mn could independently promote dendritic cell (DC) maturation, contributing to T-cell activation; (2) Mn and Que could independently facilitate M1 macrophage polarization, thereby recruiting T cells to tumors by secreting immune cytokines; (3) Que loaded HA-MSN(Mn) downregulates PD-L1 expression on tumor cells, overcoming immune escape and enhancing T cell cytotoxicity. Furthermore, the nanoplatform exhibits antitumor effects associated with immune modulation, alongside enhanced inhibition of tumor growth, with minimal off-target toxicity. Importantly, this study provides deeper insights into the multi-immunomodulatory role of quercetin, offering a promising nanotechnology-driven approach for immunotherapy.
如何引用
AMA
Yuqian Chen, Tong Li, Ying Zhang, Shengxiu Wen, Meijun Liu, Linlin Hu, et al. A triple-immunomodulatory quercetin nanoplatform to reinforce T-cell function and remodel tumor microenvironment.. Biomaterials advances. 2027; doi:10.1016/j.bioadv.2026.215197.
APA
Yuqian Chen, Tong Li, Ying Zhang, Shengxiu Wen, Meijun Liu, Linlin Hu, et al (2027). A triple-immunomodulatory quercetin nanoplatform to reinforce T-cell function and remodel tumor microenvironment.. Biomaterials advances. https://doi.org/10.1016/j.bioadv.2026.215197
GB/T 7714
Yuqian Chen, Tong Li, Ying Zhang, Shengxiu Wen, Meijun Liu, Linlin Hu, et al. A triple-immunomodulatory quercetin nanoplatform to reinforce T-cell function and remodel tumor microenvironment.[J]. Biomaterials advances, 2027 doi:10.1016/j.bioadv.2026.215197.
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