Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, P. R. China.
School of Life Science, Chongqing University, Chongqing 400044, P. R. China.
J Mater Chem B. 2021 May 26;9(20):4143-4153. doi: 10.1039/d1tb00528f.
Synergistic therapies, such as chemo-photodynamic therapy, have been growing fast because of their efficacy against cancers. Although metal-organic frameworks have been widely studied in the field of drug delivery, the metal-organic frameworks (MOFs) with a two-dimensional (2D) structure integrated by photosensitizers are rarely reported. However, chemo-photodynamic therapy still has limitations such as the inhibitory effect from intracellular glutathione (GSH). In this work, a simple bottom-up synthesis method was used to synthesize a pH-responsive drug delivery system with a 2D MOF structure. In particular, tetracarboxyporphyrin (TCPP) derivatives were coordinated with bivalent copper ions as organic bridging molecules in a polyvinylpyrrolidone (PVP) solution, and copper porphyrin MOFs (Cu-TCPP nanosheets) were synthesized by a hydrothermal method from bottom to top. DOX was loaded onto Cu-TCPP nanosheets by π-π stacking with a high drug loading rate of 33%. DOX@Cu-TCPP nanosheets showed pH-responsive DOX releasing behaviour and significant GSH scavenging ability. In addition, the evaluation of in vitro and in vivo treatment showed that DOX@Cu-TCPP nanosheets had high anti-tumor activity and excellent biocompatibility. Therefore, this study opens a new idea for the application of MOF nanosheets in tumor therapy and provides a supporting basis for the treatment of cancers by chemo-photodynamic synergistic therapy.
协同治疗，如化疗-光动力疗法，由于其对癌症的疗效而迅速发展。尽管金属有机骨架在药物输送领域得到了广泛的研究，但由光敏剂集成的二维（2D）结构的金属有机骨架（MOFs）很少有报道。然而，化疗-光动力疗法仍然存在一些限制，如细胞内谷胱甘肽（GSH）的抑制作用。在这项工作中，使用了一种简单的自下而上的合成方法来合成具有 2D MOF 结构的 pH 响应性药物输送系统。具体来说，四羧基卟啉（TCPP）衍生物与二价铜离子配位作为有机桥联分子在聚乙烯吡咯烷酮（PVP）溶液中，通过水热法从下到上合成铜卟啉 MOFs（Cu-TCPP 纳米片）。DOX 通过π-π堆积装载到 Cu-TCPP 纳米片上，载药率高达 33%。DOX@Cu-TCPP 纳米片表现出 pH 响应性 DOX 释放行为和显著的 GSH 清除能力。此外，体外和体内治疗评价表明，DOX@Cu-TCPP 纳米片具有高抗肿瘤活性和优异的生物相容性。因此，本研究为 MOF 纳米片在肿瘤治疗中的应用开辟了新思路，并为化疗-光动力协同治疗癌症提供了支持依据。
