You Yuanyuan, Chang Yanzhou, Pan Shuya, Bu Qingyue, Ling Jiabao, He Weiling, Chen Tianfeng
Department of Oncology and Nano-therapeutics Institute of The First Affiliated Hospital and department of chemistry, College of Chemistry and Materials Science, Jinan University, 510632, Guangzhou, China.
Department of Orthopedics of Affiliated Hospital, Department of Pharmacy, Guangdong Medical University, 524001, Zhanjiang, China.
Angew Chem Int Ed Engl. 2025 Jan 2;64(1):e202412922. doi: 10.1002/anie.202412922. Epub 2024 Oct 22.
Chalcogens are used as sensitive redox-responsive reagents in tumor therapy. However, chalcogen bonds triggered by external ionizing radiation, rather than by internal environmental stimuli, enable site-directed and real-time drug degradation in target lesions. This approach helps to bypass chemoresistance and global systemic toxicity, presenting a significant advancement over traditional chemoradiotherapy. In this study, we fabricated a hybrid monodisperse organosilica nanoprodrug based on homonuclear single bonds (disulfide bonds (S-S, approximately 240 kJ/mol), diselenium bonds (Se-Se, approximately 172 kJ/mol), and tellurium bonds (Te-Te, 126 kJ/mol)), including ditelluride-bond-bridged MONs (DTeMSNs), diselenide-bond-bridged MONs (DSeMSNs) and disulfide-bond-bridged MONs (DSMSNs). The results demonstrated that differences in electronegativities and atomic radii influenced their oxidation sensitivities and reactivities. Tellurium, with the lowest electronegativity, showed the highest sensitivity, followed by selenium and sulfur. DTeMSNs exhibited highly responsive cleavage upon exposure to X-rays, resulting in oxidation to TeO . Furthermore, chalcogen-hybridized organosilica was loaded with manganese ions (Mn) to enhance the release of Mn during radiotherapy, thereby activating the the stimulator of interferon genes (STING) pathway and enhancing the tumor immune response to inhibit tumor growth. This investigation of hybrid organosilica deepens our understanding of chalcogens response characteristics to radiotherapy and enriches the design principles for nanomedicine based on prodrugs.
氧族元素在肿瘤治疗中用作敏感的氧化还原响应试剂。然而，由外部电离辐射而非内部环境刺激引发的氧族元素键，能够在靶病变部位实现定点和实时药物降解。这种方法有助于绕过化疗耐药性和全身性毒性，相较于传统放化疗有显著进步。在本研究中，我们基于同核单键（二硫键（S-S，约240 kJ/mol）、二硒键（Se-Se，约172 kJ/mol）和碲键（Te-Te，126 kJ/mol））制备了一种混合单分散有机硅纳米前药，包括碲键桥连的MONs（DTeMSNs）、二硒键桥连的MONs（DSeMSNs）和二硫键桥连的MONs（DSMSNs）。结果表明，电负性和原子半径的差异影响了它们的氧化敏感性和反应活性。电负性最低的碲表现出最高的敏感性，其次是硒和硫。DTeMSNs在暴露于X射线时表现出高度响应性裂解，氧化生成TeO 。此外，将氧族元素杂化的有机硅负载锰离子（Mn）以增强放疗期间Mn的释放，从而激活干扰素基因刺激因子（STING）通路并增强肿瘤免疫反应以抑制肿瘤生长。这项对杂化有机硅的研究加深了我们对氧族元素对放疗响应特性的理解，并丰富了基于前药的纳米医学设计原则。
