Zhang Ni, Ping Wei, Xiang Jingfeng, Chu Sitong, Li Dan, Ning Shipeng, Zhu Daoming, Zeng Wen, Xu Qingyong
Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Adv Healthc Mater. 2025 Mar;14(8):e2401362. doi: 10.1002/adhm.202401362. Epub 2024 Oct 3.
Cold exposure (CE) therapy is an innovative and cost-efficient cancer treatment that activates brown adipose tissue to compete for glucose uptake, leading to metabolic starvation in tumors. Exploring the combined antitumor mechanisms of CE and traditional therapies (such as nanocatalysis) is exciting and promising. In this study, a platelet membrane biomimetic single-atom nanozyme (SAEs) nanodrug (PFB) carrying bis-2-(5-phenylacetamido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide (BPTES) is developed for use in cancer CE therapy. Owing to the platelet membrane modification, PFB can effectively target tumors. Upon entering cancer cells, the dual starvation effect induced by CE treatment and BPTES can significantly diminish intracellular glucose and ATP levels, resulting in a substantial reduction in cellular (glutathione) GSH, which can enhance the cytotoxic efficacy of reactive oxygen species generated by SAEs. This strategy not only boosts ROS production in tumors, but also strengthens immune responses, particularly by increasing memory T-cell abundance and suppressing distant tumor growth and tumor metastasis. Compared with SAEs therapy alone, this combined approach offers superior benefits for tumor immunotherapy. This study achieves a combination of CE and nanomedicines for the first time, providing new ideas for future nanomedicine combination therapy modalities.
冷暴露（CE）疗法是一种创新且经济高效的癌症治疗方法，它能激活棕色脂肪组织以竞争葡萄糖摄取，从而导致肿瘤发生代谢性饥饿。探索CE与传统疗法（如纳米催化）联合的抗肿瘤机制令人兴奋且前景广阔。在本研究中，开发了一种负载双 - 2 -（5 - 苯乙酰胺基 - 1,2,4 - 噻二唑 - 2 - 基）乙硫醚（BPTES）的血小板膜仿生单原子纳米酶（SAEs）纳米药物（PFB），用于癌症CE治疗。由于进行了血小板膜修饰，PFB能够有效靶向肿瘤。进入癌细胞后，CE治疗和BPTES诱导的双重饥饿效应可显著降低细胞内葡萄糖和ATP水平，导致细胞内（谷胱甘肽）GSH大量减少，这可增强SAEs产生的活性氧的细胞毒性作用。该策略不仅能促进肿瘤中ROS的产生，还能增强免疫反应，特别是通过增加记忆T细胞丰度以及抑制远处肿瘤生长和肿瘤转移。与单独使用SAEs治疗相比，这种联合方法为肿瘤免疫治疗带来了更优越的效果。本研究首次实现了CE与纳米药物的联合，为未来纳米药物联合治疗模式提供了新思路。
