Hierarchical MOF-on-MOF Architecture for pH/GSH-Controlled Drug Delivery and Fe-Based Chemodynamic Therapy,Inorganic Chemistry

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Hierarchical MOF-on-MOF Architecture for pH/GSH-Controlled Drug Delivery and Fe-Based Chemodynamic Therapy
Inorganic Chemistry ( IF 4.3 ) Pub Date : 2022-02-09 , DOI: 10.1021/acs.inorgchem.1c03855
Weishu Ni ₁ , Ling Zhang ₂ , Hengrui Zhang ₁ , Chenghui Zhang ₁ , Ke Jiang _{1,

3} , Xianying Cao _{1,

4}

Affiliation

Chemotherapy is still an important and effective clinical treatment for cancer. However, individual drugs hardly achieve precise controlled release and targeted therapy, thus resulting in unavoidable side effects. Fortunately, the emergence of drug carriers is expected to solve the above problems. In this work, the MOF-on-MOF strategy was adopted to encapsulate DOX into double-layer NH₂-MIL-88B to fabricate a core–shell-structured DOX@NH₂-MIL-88B-On-NH₂-MIL-88B (DMM) and then realize the pH and GSH dual-responsive controlled DOX release. Because of the core–shell structure, the drug-loading capacity of DMM reached 14.4 wt %, which was nearly twice that of DOX@NH₂-MIL-88B (DM), and the controlled release performance of DMM was also improved at the same time, greatly improving the kinetics equilibrium time of DOX from 2 h (DM) to 16 h (DMM) at pH 5.0. Moreover, we found that DMM also possessed peroxidase-like catalytic activity under acidic conditions, which could catalyze H₂O₂ to produce ^•OH, exhibiting the potential chemodynamical treatment of cancer. Cell experiments showed that DMM had a significant inhibitory effect against 4T1 cancer cells, and the survival rate of 4T1 cells was less than 20% at 100 ppm.

中文翻译：

用于 pH/GSH 控制的药物输送和铁基化学动力学治疗的分层 MOF-on-MOF 架构

化疗仍然是临床上重要且有效的癌症治疗方法。然而，个别药物很难实现精准控释和靶向治疗，从而导致不可避免的副作用。幸运的是，药物载体的出现有望解决上述问题。本工作采用MOF-on-MOF策略将DOX封装到双层NH ₂ -MIL-88B中，制备核壳结构的DOX@NH ₂ -MIL-88B-On-NH ₂ -MIL- 88B(DMM)进而实现pH和GSH双响应控制DOX释放。由于具有核壳结构，DMM的载药量达到14.4 wt%，几乎是DOX@NH ₂ -MIL-88B（DM）的两倍，并且DMM的控释性能也得到了提高。同时，在pH 5.0下，DOX的动力学平衡时间从2小时（DM）大大提高到16小时（DMM）。此外，我们发现DMM在酸性条件下还具有类似过氧化物酶的催化活性，可以催化H ₂ O ₂产生^· OH，展现出潜在的化学动力学治疗癌症的潜力。细胞实验表明，DMM对4T1癌细胞有显着的抑制作用，100 ppm时4T1细胞的存活率低于20%。

更新日期：2022-02-09

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