Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei Key Laboratory of Precise Imaging of Inflammation Related Tumors, College of Chemistry and Materials Science, Institute of Life Science and Green Development, Hebei University, Baoding 071002, PR China; Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, PR China.
Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei Key Laboratory of Precise Imaging of Inflammation Related Tumors, College of Chemistry and Materials Science, Institute of Life Science and Green Development, Hebei University, Baoding 071002, PR China.
J Colloid Interface Sci. 2024 Feb 15;656:93-103. doi: 10.1016/j.jcis.2023.11.086. Epub 2023 Nov 17.
As an endogenous catalytic treatment, chemodynamic therapy (CDT) was attracting considerable attention, but the weak catalytic efficiency of Fenton agents and the non-degradation of nanocarriers severely limited its development. In this work, a biodegradable bimetallic nanoreactor was developed for boosting CDT, in which Fe-doped hollow mesoporous manganese dioxide (HMnO) was selected as nanocarrier, and the Fe/HMnO@DOX-GOD@HA nanoprobe was constructed by loading doxorubicin (DOX) and modifying glucose oxidase (GOD) and hyaluronic acid (HA). The glutathione (GSH) responsive degradation of HMnO promoted the release of DOX, by which the release rate significantly increased to 96.6%. Moreover, by the GSH depletion, the reduction of Mn/Fe achieved strong bimetallic Fenton efficiency, and the hydroxyl radicals (·OH) generation was further enhanced using the self-supplying HO of GOD. Through the active targeting recognition of HA, the bimetallic nanoreactor significantly enriched the tumor accumulation, by which the enhanced antitumor efficacy was realized. Thus, this work developed biodegradable bimetallic nanoreactor by consuming GSH and self-supplying HO, and provided a new paradigm for enhancing CDT.
作为一种内源性催化治疗方法，化学动力学治疗（CDT）引起了相当大的关注，但芬顿试剂的催化效率较弱和纳米载体的不可降解性严重限制了其发展。在这项工作中，开发了一种可生物降解的双金属纳米反应器来增强 CDT，其中选择了掺杂铁的中空介孔二氧化锰（HMnO）作为纳米载体，并通过装载阿霉素（DOX）和修饰葡萄糖氧化酶（GOD）和透明质酸（HA）构建了 Fe/HMnO@DOX-GOD@HA 纳米探针。谷胱甘肽（GSH）响应性的 HMnO 降解促进了 DOX 的释放，其释放速率显著增加至 96.6%。此外，通过 GSH 的耗竭，实现了强双金属芬顿效率的 Mn/Fe 还原，并且通过 GOD 自身供应的 HO 进一步增强了羟基自由基（·OH）的生成。通过 HA 的主动靶向识别，双金属纳米反应器显著增加了肿瘤的积累，从而实现了增强的抗肿瘤疗效。因此，本工作通过消耗 GSH 和自身供应 HO 开发了可生物降解的双金属纳米反应器，为增强 CDT 提供了一种新范例。
