Highly Efficient Encapsulation of Doxorubicin Hydrochloride in Metal–Organic Frameworks for Synergistic Chemotherapy and Chemodynamic Therapy,ACS Biomaterials Science & Engineering

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Highly Efficient Encapsulation of Doxorubicin Hydrochloride in Metal–Organic Frameworks for Synergistic Chemotherapy and Chemodynamic Therapy
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2021-09-22 , DOI: 10.1021/acsbiomaterials.1c00874
Lijia Yao ₁ , Ying Tang ₁ , Wenqian Cao ₁ , Yuanjing Cui ₁ , Guodong Qian ₁

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Iron-based metal–organic frameworks (MOFs) have been reported to have great potential for encapsulating doxorubicin hydrochloride (DOX), which is a frequently used anthracycline anticancer drug. However, developing a facile approach to realize high loading capacity and efficiency as well as controlled release of DOX in MOFs remains a huge challenge. Herein, we synthesized water-stable MIL-101(Fe)-C₄H₄ through a microwave-assisted method. It was found the nano-MOFs acted as nanosponges when soaked in a DOX alkaline aqueous solution with a loading capacity experimentally up to 24.5 wt %, while maintaininga loading efficiency as high as 98%. The mechanism of the interaction between DOX and nanoMOFs was investigated by absorption spectra and density functional theory (DFT) calculations, which revealed that the deprotonated DOX was electrostatically adsorbed to the unsaturated Fe₃OCl(COO)₆·H₂O (named Fe₃ trimers). In addition, the as-designed poly(ethylene glycol-co-propylene glycol) (F127) modified nanoparticles (F127-DOX-MIL) could be decomposed under the stimulation of glutathione (GSH) and ATP. As a result, DOX and Fe(III) ions were released, and they could undergo a Fenton-like reaction with the endogenous H₂O₂ to generate the highly toxic hydroxyl radical (·OH). The in vitro experiments indicated that F127-DOX-MIL could cause remarkable Hela cells inhibition through chemotherapy and chemodynamic therapy. Our study provides a new strategy to design a GSH/ATP-responsive drug-delivery nanosystem for chemo/chemodynamic therapy.

中文翻译：

用于协同化疗和化学动力学治疗的金属-有机框架中盐酸多柔比星的高效包封

据报道，铁基金属有机骨架（MOFs）在包封盐酸多柔比星（DOX）方面具有巨大潜力，DOX是一种常用的蒽环类抗癌药物。然而，开发一种简便的方法来实现高负载能力和效率以及在 MOF 中控制 DOX 的释放仍然是一个巨大的挑战。在此，我们合成了水稳定的 MIL-101(Fe)-C ₄ H ₄通过微波辅助的方法。发现当浸泡在 DOX 碱性水溶液中时，纳米 MOF 充当纳米海绵，实验负载能力高达 24.5 wt%，同时保持高达 98% 的负载效率。通过吸收光谱和密度泛函理论（DFT）计算研究了 DOX 与 nanoMOFs 相互作用的机制，结果表明去质子化的 DOX 静电吸附到不饱和 Fe ₃ OCl(COO) ₆ ·H ₂ O（命名为 Fe ₃三聚体）。此外，作为设计的聚（乙二醇-共-丙二醇) (F127) 修饰的纳米粒子 (F127-DOX-MIL) 在谷胱甘肽 (GSH) 和 ATP 的刺激下可以分解。结果，释放出DOX和Fe(III)离子，它们与内源性H ₂ O ₂发生类芬顿反应，生成剧毒的羟基自由基(·OH)。体外实验表明，F127-DOX-MIL可通过化疗和化学动力学治疗对Hela细胞产生显着的抑制作用。我们的研究为设计用于化学/化学动力学治疗的 GSH/ATP 响应药物递送纳米系统提供了一种新策略。

更新日期：2021-10-12

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