Yang Yu, Liu Bo, Liu Yuan, Chen Jingqi, Sun Yujia, Pan Xiaoshu, Xu Jun, Xu Shujuan, Liu Zhuang, Tan Weihong
Institute of Molecular Medicine (IMM), Renji Hospital, Shanghai Jiao Tong University School of Medicine, and College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Department of Chemistry, Center for Research at Bio/Nano Interface, Department of Physiology and Functional Genomics, Health Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200, United States.
Nano Lett. 2022 Apr 13;22(7):2826-2834. doi: 10.1021/acs.nanolett.1c04888. Epub 2022 Mar 28.
Metal "X" Frameworks (MXFs) constructed from metal ions and biomacromolecules ("X components") via coordination interactions show crystalline structures and diverse functionalities. Here, a series of MXFs composed of various metal ions (e.g., Zn, Hf, Ca) and DNA oligodeoxynucleotides were reported. With MXF consisting of Hf and CpG oligodeoxynucleotides as the example, we show that such Hf-CpG MXF can achieve high-Z elements-enhanced photon radiotherapy and further trigger robust tumor-specific immune responses, thus showing efficient tumor suppression ability. experiments showed that external beam radiotherapy applied on tumors locally injected with Hf-CpG MXF result in the thorough elimination of primary tumors, complete inhibition of tumor metastasis, and protection against tumor rechallenge by triggering robust antitumor immune responses. Our findings provide a blueprint for fabricating a variety of rationally designed MXFs with desired functions and present the strategy of stimulating whole-body systemic immune responses by only local treatment of radiotherapy.
通过配位相互作用由金属离子和生物大分子(“X 组分”)构建的金属“X”框架(MXFs)呈现出晶体结构和多样的功能。在此,报道了一系列由各种金属离子(如锌、铪、钙)和 DNA 寡聚脱氧核苷酸组成的 MXFs。以由铪和 CpG 寡聚脱氧核苷酸组成的 MXF 为例,我们表明这种铪-CpG MXF 能够实现高 Z 元素增强的光子放射治疗,并进一步触发强大的肿瘤特异性免疫反应,从而显示出有效的肿瘤抑制能力。实验表明,对局部注射了铪-CpG MXF 的肿瘤进行外照射放疗,通过触发强大的抗肿瘤免疫反应,可彻底消除原发性肿瘤、完全抑制肿瘤转移并预防肿瘤再次攻击。我们的研究结果为制造具有所需功能的各种合理设计的 MXFs 提供了蓝图,并提出了仅通过局部放疗来刺激全身系统性免疫反应的策略。