Du Qijun, Wu Guohua, Xie Ao, Wu Di, Hu Wenqi, Lu Qinrui, Liu Jie, Wang Jiashu, Yang Youlong, Hu Bangchuan, Hu Haijie, Wang Shuqi
College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China.
J Mater Chem B. 2025 Aug 6;13(31):9418-9429. doi: 10.1039/d5tb00926j.
Radiotherapy (RT) faces hypoxia-induced radioresistance, as oxygen-deficient tumor regions limit reactive oxygen species (ROS) generation. Current hypoxia-targeting strategies (, prodrugs, nanocarriers) struggle with inefficient delivery, off-target effects, and clinical translation barriers, necessitating advanced oxygenation or hypoxia-specific radiosensitization approaches. Herein, we developed pH-responsive BM-DOX@BSA nanoparticles (NPs) using a solvothermal method. Bi(NO), MnCl, and TCPP were used as precursors, with DOX loaded for chemotherapy. BSA was added to enhance biocompatibility. and experiments assessed ROS generation, drug release, cytotoxicity, and tumor suppression efficacy under X-ray irradiation. BM-DOX@BSA NPs exhibited pH-responsive degradation, releasing DOX more rapidly in acidic conditions. They markedly increased the generation of ROS under X-ray irradiation, resulting in enhanced apoptosis of tumor cells and DNA damage. This effectively improved the efficacy of radiation dynamic therapy (RDT). , the NPs combined with RT achieved 100% tumor suppression in HepG2 tumor-bearing mice, demonstrating excellent biocompatibility and therapeutic efficacy.
放射治疗（RT）面临缺氧诱导的放射抗性，因为缺氧的肿瘤区域会限制活性氧（ROS）的产生。当前的缺氧靶向策略（如前药、纳米载体）存在递送效率低下、脱靶效应和临床转化障碍等问题，因此需要先进的氧合或缺氧特异性放射增敏方法。在此，我们使用溶剂热法制备了pH响应性的BM-DOX@BSA纳米颗粒（NPs）。以Bi(NO)、MnCl和TCPP为前驱体，负载阿霉素（DOX）用于化疗。添加牛血清白蛋白（BSA）以增强生物相容性。通过实验评估了在X射线照射下ROS的产生、药物释放、细胞毒性和肿瘤抑制效果。BM-DOX@BSA NPs表现出pH响应性降解，在酸性条件下更快速地释放DOX。它们在X射线照射下显著增加了ROS的产生，导致肿瘤细胞凋亡增强和DNA损伤。这有效地提高了放射动力疗法（RDT）的疗效。此外，NPs与RT联合使用在荷HepG2肿瘤小鼠中实现了100%的肿瘤抑制，显示出优异的生物相容性和治疗效果。
