Chang Yanzhou, Huang Jiarun, Shi Sujiang, Xu Ligeng, Lin Hao, Chen Tianfeng
Department of Chemistry, College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Functional Supramolecular Coordination Materials and Applications, Jinan University, Guangzhou, 510632, China.
Department of Orthopedics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
Adv Mater. 2023 Sep;35(36):e2212178. doi: 10.1002/adma.202212178. Epub 2023 Jul 21.
Facilely synthesized nanoradiosensitizers with well-controlled structure and multifunctionality are greatly desired to address the challenges of cancer radiotherapy. In this work, a universal method is developed for synthesizing chalcogen-based TeSe nano-heterojunctions (NHJs) with rod-, spindle-, or dumbbell-like morphologies by engineering the surfactant and added selenite. Interestingly, dumbbell-shaped TeSe NHJs (TeSe NDs) as chaperone exhibit better radio-sensitizing activities than the other two nanostructural shapes. Meanwhile, TeSe NDs can serve as cytotoxic chemodrugs that degrade to highly toxic metabolites in acidic environment and deplete GSH within tumor to facilitate radiotherapy. More importantly, the combination of TeSe NDs with radiotherapy significantly decreases regulatory T cells and M2-phenotype tumor-associated macrophage infiltrations within tumors to reshape the immunosuppressive microenvironment and induce robust T lymphocytes-mediated antitumor immunity, resulting in great abscopal effects on combating distant tumor progression. This study provides a universal method for preparing NHJ with well-controlled structure and developing nanoradiosensitizers to overcome the clinical challenges of cancer radiotherapy.
为应对癌症放射治疗的挑战，人们迫切需要轻松合成具有结构可控和多功能性的纳米放射增敏剂。在这项工作中，通过设计表面活性剂和添加亚硒酸盐，开发了一种通用方法来合成具有棒状、纺锤状或哑铃状形态的基于硫属元素的碲硒纳米异质结（NHJ）。有趣的是，作为伴侣的哑铃状碲硒NHJ（TeSe ND）比其他两种纳米结构形状表现出更好的放射增敏活性。同时，TeSe ND可作为细胞毒性化学药物，在酸性环境中降解为高毒代谢物，并消耗肿瘤内的谷胱甘肽以促进放射治疗。更重要的是，TeSe ND与放射治疗的联合显著减少肿瘤内调节性T细胞和M2表型肿瘤相关巨噬细胞浸润，以重塑免疫抑制微环境并诱导强大的T淋巴细胞介导的抗肿瘤免疫，从而对对抗远处肿瘤进展产生巨大的远隔效应。本研究提供了一种制备结构可控的NHJ和开发纳米放射增敏剂的通用方法，以克服癌症放射治疗的临床挑战。
