ZnO–DOX@ZIF-8 Core–Shell Nanoparticles for pH-Responsive Drug Delivery,ACS Biomaterials Science & Engineering

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ZnO–DOX@ZIF-8 Core–Shell Nanoparticles for pH-Responsive Drug Delivery
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2017-08-18 00:00:00 , DOI: 10.1021/acsbiomaterials.7b00435
Cunchuan Zheng _{1,

2} , Yang Wang ₂ , Soo Zeng Fiona Phua ₂ , Wei Qi Lim ₂ , Yanli Zhao _{2,

3}

Affiliation

Developing multifunctional hybrid nanosystems for controlled drug delivery is a challenging task. In this work, we prepared hierarchical core–shell nanoparticles (ZnO–DOX@ZIF-8) composed of mesoporous ZnO core and microporous ZIF-8 shell, in which the core serves as the drug storage reservoir for the loading of anticancer drug doxorubicin (DOX) and the shell could be used to prevent premature release of loaded drug at physiological environment. The mesoporous ZnO nanoparticles were first prepared, followed by DOX drug loading. Such ZnO nanoparticles were then employed as the zinc source to react with 2-methylimidazole for the formation of ZnO–DOX@ZIF-8 core–shell nanoparticles. The core–shell nanoparticles exhibit good dispersibility and stability as well as pH-responsive drug release property. While only up to 20% of loaded DOX was released in the buffer of pH 7.4, over 80% of DOX was released in the buffer of pH 5.5 because of the decomposition of the ZIF-8 shell as well as the dissolution of the ZnO core under acidic conditions. The confocal microscopy studies show that the core–shell nanoparticles could be efficiently internalized by cancer cells, and the loaded DOX in the nanoparticles could be successfully released under acidic intracellular environment. The in vitro cytotoxicity measurements demonstrate that the core–shell nanoparticles free of drug exhibit a significant cytotoxicity when the concentration was above 25 μg/mL on account of the production of reactive oxygen species. The reactive oxygen species are only generated in acidic condition, which could combine with DOX for a synergistic cancer treatment with satisfactory therapeutic efficacy. On the other hand, the nanoparticles were stable and nontoxic in physiological environment. Thus, the ZnO–DOX@ZIF-8 core–shell nanoparticles are a promising pH-responsive drug delivery system for the cancer therapy.

中文翻译：

ZnO–DOX @ ZIF-8核壳纳米粒子，用于pH响应药物递送

开发用于控制药物输送的多功能杂化纳米系统是一项艰巨的任务。在这项工作中，我们制备了由介孔ZnO核和微孔ZIF-8壳组成的分层核-壳纳米颗粒（ZnO-DOX @ ZIF-8），其中核充当了储存抗癌药物阿霉素（ DOX）和外壳可用于防止在生理环境中过早释放负载的药物。首先制备介孔ZnO纳米粒子，然后进行DOX药物装载。然后将此类ZnO纳米颗粒用作锌源，与2-甲基咪唑反应形成ZnO–DOX @ ZIF-8核－壳纳米颗粒。核壳纳米粒子具有良好的分散性和稳定性，以及对pH敏感的药物释放特性。虽然在pH 7.4的缓冲液中仅释放高达20％的负载DOX，但由于ZIF-8壳的分解以及ZnO核心的溶解，在pH 5.5的缓冲液中却释放了超过80％的DOX。在酸性条件下。共聚焦显微镜研究表明，核壳纳米颗粒可以被癌细胞有效地内化，纳米颗粒中负载的DOX可以在酸性细胞内环境下成功释放。体外细胞毒性测量结果表明，由于活性氧的产生，当浓度高于25μg/ mL时，不含药物的核壳纳米颗粒表现出显着的细胞毒性。活性氧仅在酸性条件下产生，可以与DOX联合使用以达到令人满意的疗效，进行协同性癌症治疗。另一方面，纳米颗粒在生理环境中稳定且无毒。因此，ZnO–DOX @ ZIF-8核壳纳米粒子是用于癌症治疗的有希望的pH响应药物递送系统。

更新日期：2017-08-19

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