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      A phosphorylcholine-based zwitterionic copolymer coated ZIF-8 nanodrug with a long circulation time and charged conversion for enhanced chemotherapy.

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          Abstract

          In recent years, zeolitic imidazolate framework-8 (ZIF-8) has become an attractive metal organic framework (MOF) material in drug delivery for cancer chemotherapy. However, as a drug delivery system, ZIF-8 still shows some disadvantages, such as short blood circulation time and poor tumor targeting, leading to reduced drug delivery efficiency and unsatisfactory treatment. Herein, we developed a phosphorylcholine-based zwitterionic copolymer coated ZIF-8 nanodrug (DOX@ZIF-8@P(MPC-co-C7A)), and the obtained nanodrug was prepared via a charge-conversional zwitterionic copolymer coating on DOX@ZIF-8 composites. In this system, DOX was encapsulated in the framework of ZIF-8, which could reduce the drug leakage in the bloodstream. The phosphorylcholine-based zwitterionic copolymer effectively extended the blood circulation time, resulting in enhanced tumor accumulation of the nanodrug. Once the nanodrug reached the tumor site, the surface charge of the system could rapidly convert to positive, resulting in an enhanced tumor cellular uptake. Finally, in the acidic environment inside intracellular organelles, DOX will be released rapidly for chemotherapy owing to the fast disintegration of ZIF-8 frameworks. Therefore, the obtained nanodrug could effectively inhibit the growth of A549-bearing tumors (93.2% tumor inhibition rate) with negligible side effects. Overall, this work significantly improved the drug delivery efficiency of ZIF-8, which may pave the way for the biomedical applications of ZIF-8 crystals in anti-tumor drug delivery.

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          Author and article information

          Journal
          J Mater Chem B
          Journal of materials chemistry. B
          Royal Society of Chemistry (RSC)
          2050-7518
          2050-750X
          July 28 2020
          : 8
          : 28
          Affiliations
          [1 ] State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, No. 220 Handan Road, Shanghai 200433, P. R. China. wlyang@fudan.edu.cn.
          Article
          10.1039/d0tb00193g
          32568335
          e7bcac90-ca52-4cb0-84ad-d2f4174abb39
          History

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