Shi Linlin, Yu Ying, Li Jiayi, Ma Beng, Zhang Xiaoman, Yang Pingjuan, Chen Pan, Qu Zhifeng, Zhang Fengqi, Liu Ke, Gao Shegan, Cheng Haoyan
Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Cancer Epigenetics, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471003, China.
School of Materials Science and Engineering, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471023, China.
J Nanobiotechnology. 2025 May 17;23(1):356. doi: 10.1186/s12951-025-03434-7.
Esophageal cancer (EC) represents a highly recurrent and aggressive malignancy within the digestive system. However, conventional therapeutic strategies exhibit notable limitations in their clinical applications. Photothermal therapy (PTT), combined with ferroptosis, has attracted considerable attentions, emerging as a promising novel strategy for EC treatment. Therefore, there is a critical need to develop a drug delivery system capable of effectively integrating these two therapeutic approaches. In this work, we report a novel drug delivery system based on ferrocene (Fc), which is mixed with lauric acid (a phase-change material with a melting point around 44 C) and then coated on the surface of CuSe nanoparticles. The photothermal properties of CuSe triggers the melting of lauric acid under near-infrared (NIR) laser irradiation, facilitating controlled release of Fc. Following internalization by tumor cells via endocytosis, the synergistic effect of PTT and ferroptosis, triggered by CuSe@Fc, induced immunogenic cell death, which promoted dendritic cell maturation and cytotoxic T lymphocytes recruitment while decreasing the proportion of regulatory T cells, thereby strengthening the antitumor immune surveillance and improving the therapeutic efficacy of Anti-PD-1 blockade. These findings propose that the NIR-responsive CuSe@Fc formulation represents a promising and effective strategy with prospecting application for cancer treatment.
食管癌（EC）是消化系统中一种具有高度复发性和侵袭性的恶性肿瘤。然而，传统的治疗策略在临床应用中存在显著局限性。光热疗法（PTT）与铁死亡相结合，已引起了广泛关注，成为一种有前景的食管癌治疗新策略。因此，迫切需要开发一种能够有效整合这两种治疗方法的药物递送系统。在这项工作中，我们报道了一种基于二茂铁（Fc）的新型药物递送系统，它与月桂酸（一种熔点约为44℃的相变材料）混合，然后包覆在硒化铜纳米颗粒表面。硒化铜的光热性质在近红外（NIR）激光照射下触发月桂酸熔化，促进二茂铁的控释。通过内吞作用被肿瘤细胞摄取后，CuSe@Fc触发的PTT和铁死亡的协同效应诱导免疫原性细胞死亡，促进树突状细胞成熟和细胞毒性T淋巴细胞募集，同时降低调节性T细胞比例，从而加强抗肿瘤免疫监视并提高抗程序性死亡蛋白1（Anti-PD-1）阻断的治疗效果。这些发现表明，近红外响应性CuSe@Fc制剂是一种有前景且有效的策略，在癌症治疗中具有潜在应用价值。
