Li Honghui, Zhang Ying, Liang Lingxia, Song Jiaxing, Wei Zixuan, Yang Shuyue, Ma Yunong, Chen Wei R, Lu Cuixia, Wen Liewei
Medical College, Guangxi University, Nanning 530004, China.
Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with JinanUniversity), Jinan University, Zhuhai 519000, China.
Materials (Basel). 2022 Jan 30;15(3):1096. doi: 10.3390/ma15031096.
Doxorubicin (DOX) is a widely used first-line antitumor agent; however, acquired drug resistance and side effects have become the main challenges to effective cancer therapy. Herein, DOX is loaded into iron-rich metal-organic framework/tannic acid (TA) nanocomplex to form a tumor-targeting and acid-activatable drug delivery system (MOF/TA-DOX, MTD). Under the acidic tumor microenvironment, MTD simultaneously releases DOX and ferrous ion (Fe) accompanied by degradation. Apart from the chemotherapeutic effect, DOX elevates the intracellular HO levels through cascade reactions, which will be beneficial to the Fenton reaction between the Fe and HO, to persistently produce hydroxyl radicals (•OH). Thus, MTD efficiently mediates chemodynamic therapy (CDT) and remarkably enhances the sensitivity of chemotherapy. More encouragingly, the cancer cell killing efficiency of MTD is up to ~86% even at the ultralow equivalent concentration of DOX (2.26 μg/mL), while the viability of normal cells remained >88% at the same concentration of MTD. Taken together, MTD is expected to serve as drug-delivery nanoplatforms and •OH nanogenerators for improving chemo/chemodynamic synergistic therapy and reducing the toxic side effects.
阿霉素（DOX）是一种广泛使用的一线抗肿瘤药物；然而，获得性耐药和副作用已成为有效癌症治疗的主要挑战。在此，将DOX负载到富含铁的金属有机框架/单宁酸（TA）纳米复合物中，形成一种肿瘤靶向和酸激活的药物递送系统（MOF/TA-DOX，MTD）。在酸性肿瘤微环境下，MTD伴随降解同时释放DOX和亚铁离子（Fe）。除了化疗作用外，DOX通过级联反应提高细胞内HO水平，这将有利于Fe与HO之间的芬顿反应，持续产生羟基自由基（•OH）。因此，MTD有效地介导了化学动力学疗法（CDT），并显著提高了化疗的敏感性。更令人鼓舞的是，即使在DOX的超低等效浓度（2.26μg/mL）下，MTD对癌细胞的杀伤效率也高达约86%，而在相同浓度的MTD下，正常细胞的存活率仍>88%。综上所述，MTD有望作为药物递送纳米平台和•OH纳米发生器，用于改善化疗/化学动力学协同治疗并减少毒副作用。
