卟啉基金属有机框架负载高铁酸钾:光-化学动力学联合治疗肿瘤性能研究

Potassium Ferrate-loaded Porphyrin-based(Ⅵ)Metal-organic Frameworks for Combined Photodymanic and Chemodynamic Tumor Therapy

金属有机框架因具有多孔结构、高比表面积、丰富的官能团和金属活性位点以及良好的生物相容性和降解性而被广泛应用于生物医学领域。本研究提出以卟啉基金属有机框架纳米颗粒(PCN-224)为载体负载高化学价态的高铁酸钾氧化剂(K_(2)FeO_(4),Fe(Ⅵ)),经牛血清蛋白(BSA)包覆表面制备多功能复合纳米颗粒(Fe(Ⅵ)@PCN@BSA),用于肿瘤光–化学动力学联合治疗。实验结果表明,PCN-224纳米颗粒粒径约为90 nm,而Fe(Ⅵ)@PCN@BSA纳米颗粒粒径约为100 nm。Fe(Ⅵ)@PCN@BSA纳米颗粒在模拟肿瘤微环境条件下能够催化H_(2)O_(2)反应,产生有细胞毒性的·OH而实现化学动力学效应,同时也能够氧化分解部分H_(2)O_(2)产生O_(2),在660 nm激光照射下提高单线态氧(^(1)O_(2))产生量,增强光动力学效应。进一步细胞实验证实Fe(Ⅵ)@PCN@BSA纳米颗粒具有较好的生物相容性,能够获得增强的光–化学动力学联合治疗肿瘤效果。因此,Fe(Ⅵ)@PCN@BSA纳米颗粒在肿瘤治疗方面具有潜在的应用前景。

Metal-organic frameworks(MOFs)are widely used in biomedicine due to their porous structure,high spe-cific surface area,abundant functional groups with metal active sites,good biocompatibility,and suitable degradability.In this study,a multifunctional composite nanoparticle(Fe(Ⅵ)@PCN@BSA)was prepared for combined photody-namic and chemodynamic therapy of tumors,which was constructed by loading potassium ferrate(K_(2)FeO_(4),Fe(Ⅵ))in porphyrin-based MOFs(PCN-224)and following a surface coating with biocompatible bovine serum albumin(BSA).The results showed that the particle sizes of PCN-224 and Fe(Ⅵ)@PCN@BSA nanoparticles were about 90 nm and 100 nm,respectively.Interestingly,Fe(Ⅵ)@PCN@BSA nanoparticles could catalyze H_(2)O_(2) to produce·OH under a simulating tumor environmental condition.Meanwhile,they catalyzed to decompose H_(2)O_(2) to produce O_(2),and thereby increased the production of singlet oxygen(^(1)O_(2))under 660 nm laser irradiation,which enhanced the photodynamic effect.More importantly,in vitro evaluation indicated that Fe(Ⅵ)@PCN@BSA nanoparticles were biocompatible,and exhibited enhanced photodynamic and chemodynamic combined therapeutic efficacy against tumor cells.Hence,Fe(Ⅵ)@PCN@BSA nanoparticles have a great potential application in tumor therapy.