Ji Anqi, Yang Pingjuan, Ma Beng, Li Jiayi, Yu Ying, Zhang Xiaoman, Chen Pan, Yao Haonan, Shi Linlin, Hu Hao, Gao Shegan, Cheng Haoyan
School of Materials Science and Engineering, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471023, China.
Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471023, China.
J Colloid Interface Sci. 2025 Nov 15;698:138042. doi: 10.1016/j.jcis.2025.138042. Epub 2025 Jun 3.
The integration of photothermal therapy (PTT) with chemotherapy and immunotherapy holds great promise for improving cancer treatment efficacy, yet achieving precise control over drug release and synergistic modulation of the immunosuppressive tumor microenvironment (TME) remains challenging. Herein, we report a hollow CuS-based nanoplatform that synergistically combines NIR-triggered photothermal-chemotherapy with PD-L1 suppression for enhanced antitumor immunity. The hollow CuS nanoparticles exhibit exceptional photothermal conversion efficiency under 980 nm irradiation, while the phase-change material (PCM) of lauric acid enables controlled release of curcumin (Cur) in response to localized hyperthermia. In vitro studies demonstrate that the released Cur synergistically enhances photothermal ablation, inducing immunogenic cell death (ICD) via ROS generation, mitochondrial dysfunction, and damage-associated molecular patterns (DAMPs) release. Notably, Cur downregulates PD-L1 expression in tumor cells by inhibiting the EGFR-STAT3 signaling axis, thereby alleviating immune evasion. In vivo, the nanoplatform (CuS@PCM@Cur) shows NIR-triggered temperature elevation, achieving potent tumor growth suppression. When combined with anti-PD-1 therapy, CuS@PCM@Cur after laser irradiation further amplifies antitumor immunity by increasing cytotoxic T lymphocyte infiltration and dendritic cell maturation while reducing regulatory T cells in the TME. Comprehensive biosafety evaluations confirm minimal systemic toxicity. This work presents a rationally designed nanotherapeutic strategy that synchronizes physical ablation, chemotherapy, and immune reprogramming, offering a promising multimodal approach to combat resistant malignancies.
将光热疗法(PTT)与化疗和免疫疗法相结合,在提高癌症治疗效果方面具有巨大潜力,但实现对药物释放的精确控制以及对免疫抑制性肿瘤微环境(TME)的协同调节仍然具有挑战性。在此,我们报道了一种基于空心硫化铜的纳米平台,该平台将近红外触发的光热化疗与PD-L1抑制协同结合,以增强抗肿瘤免疫力。空心硫化铜纳米颗粒在980nm照射下表现出优异的光热转换效率,而月桂酸相变材料(PCM)能够响应局部热疗实现姜黄素(Cur)的控释。体外研究表明,释放的Cur协同增强光热消融,通过活性氧生成、线粒体功能障碍和损伤相关分子模式(DAMPs)释放诱导免疫原性细胞死亡(ICD)。值得注意的是,Cur通过抑制EGFR-STAT3信号轴下调肿瘤细胞中PD-L1的表达,从而减轻免疫逃逸。在体内,纳米平台(CuS@PCM@Cur)表现出近红外触发的温度升高,实现了有效的肿瘤生长抑制。当与抗PD-1疗法联合使用时,激光照射后的CuS@PCM@Cur通过增加细胞毒性T淋巴细胞浸润和树突状细胞成熟,同时减少TME中的调节性T细胞,进一步增强抗肿瘤免疫力。全面的生物安全性评估证实全身毒性极小。这项工作提出了一种合理设计的纳米治疗策略,该策略同步了物理消融、化疗和免疫重编程,为对抗耐药性恶性肿瘤提供了一种有前景的多模态方法。
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