有机小分子用于恶性肿瘤光热/光动力及细胞凋亡和铁下垂免疫治疗

IF 5.8 2区化学 Q1 POLYMER SCIENCE

European Polymer Journal Pub Date : 2025-05-17 DOI:10.1016/j.eurpolymj.2025.114018

Jie Zeng , Miao-Yan Xu , Xin-Hao Han , Duo-Duo Wei , Bing Fan , Xing Wang , Xin-Hui Qu , Shaorong Huang , Xiao-Jian Han

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引用次数: 0

摘要

光免疫疗法对多种恶性肿瘤的治疗具有重要的前景，但目前其疗效有待提高。本文设计并合成了一种光触发IC8纳米粒子（IC8 NPs），该纳米粒子具有良好的生物相容性和稳定性，在近红外照射下具有优异的光热转换效率（PCE = 65.27%）和I型光动力。高热和活性氧（ROS）的富集会引起显著的细胞氧化损伤并引发严重的细胞凋亡。另一方面，谷胱甘肽（GSH）和谷胱甘肽过氧化物酶4 （GPX4）水平下调可间接上调脂质过氧化物（LPO）水平，促进铁死亡。此外，IC8 NPs + NIR不仅可以显著消融原发肿瘤，还可以诱导免疫原性细胞死亡（ICD），从而促进树突状细胞（dc）的成熟，并激活效应细胞，从而强烈地激发抗肿瘤免疫反应，用于远处肿瘤的治疗。本研究为改善恶性肿瘤治疗提供了光热/光动力和光免疫治疗的新纳米平台。

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Organic small molecule for malignant tumor photothermal / photodynamic and immunotherapy via apoptosis and ferroptosis

Photoimmunotherapy holds significant promise for addressing diverse malignant tumors, at present, its efficacy needs to be improved. Herein, a light-triggered IC8 nanoparticles (IC8 NPs) were designed and synthesized which possess excellent biocompatibility, stability and upon the NIR irradiation has superior photothermal convert efficiency (PCE = 65.27 %) and Type I photodynamic. The enrichment of hyperthermia and reactive oxygen species (ROS) causes significant oxidative cellular damage and triggers severe apoptosis. In another aspect, the glutathione (GSH) and glutathione peroxidase 4 (GPX4) level down-regulated can indirectly upregulate the level of lipid peroxides (LPO) and promote ferroptosis. Moreover, IC8 NPs + NIR could not only significantly ablate primary tumor but also induce immunogenic cell death (ICD), which promote maturation of dendritic cells (DCs) and activate effector cells that robustly evoke the antitumor immune responses for distant tumors treatment. This study offers a new nanoplatform as photothermal/photodynamic and photoimmunotherapy to improve malignant tumor therapy.

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来源期刊

European Polymer Journal 化学-高分子科学

CiteScore

9.90

自引率

10.00%

发文量

691

审稿时长

23 days

期刊介绍： European Polymer Journal is dedicated to publishing work on fundamental and applied polymer chemistry and macromolecular materials. The journal covers all aspects of polymer synthesis, including polymerization mechanisms and chemical functional transformations, with a focus on novel polymers and the relationships between molecular structure and polymer properties. In addition, we welcome submissions on bio-based or renewable polymers, stimuli-responsive systems and polymer bio-hybrids. European Polymer Journal also publishes research on the biomedical application of polymers, including drug delivery and regenerative medicine. The main scope is covered but not limited to the following core research areas: Polymer synthesis and functionalization • Novel synthetic routes for polymerization, functional modification, controlled/living polymerization and precision polymers. Stimuli-responsive polymers • Including shape memory and self-healing polymers. Supramolecular polymers and self-assembly • Molecular recognition and higher order polymer structures. Renewable and sustainable polymers • Bio-based, biodegradable and anti-microbial polymers and polymeric bio-nanocomposites. Polymers at interfaces and surfaces • Chemistry and engineering of surfaces with biological relevance, including patterning, antifouling polymers and polymers for membrane applications. Biomedical applications and nanomedicine • Polymers for regenerative medicine, drug delivery molecular release and gene therapy The scope of European Polymer Journal no longer includes Polymer Physics.