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

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

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.