Sustained and targeted delivery of checkpoint inhibitors by metal-organic frameworks for cancer immunotherapy

通过金属有机骨架持续和有针对性地递送检查点抑制剂用于癌症免疫治疗

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作者:Shahad K Alsaiari, Somayah S Qutub, Shichao Sun, Walaa Baslyman, Mansour Aldehaiman, Mram Alyami, Abdulaziz Almalik, Rabih Halwani, Jasmeen Merzaban, Zhengwei Mao, Niveen M Khashab

Abstract

The major impediments to the implementation of cancer immunotherapies are the sustained immune effect and the targeted delivery of these therapeutics, as they have life-threatening adverse effects. In this work, biomimetic metal-organic frameworks [zeolitic imidazolate frameworks (ZIFs)] are used for the controlled delivery of nivolumab (NV), a monoclonal antibody checkpoint inhibitor that was U.S. Food and Drug Administration-approved back in 2014. The sustained release behavior of NV-ZIF has shown a higher efficacy than the naked NV to activate T cells in hematological malignancies. The system was further modified by coating NV-ZIF with cancer cell membrane to enable tumor-specific targeted delivery while treating solid tumors. We envisage that such a biocompatible and biodegradable immunotherapeutic delivery system may promote the development and the translation of hybrid superstructures into smart and personalized delivery platforms.

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