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

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.

Biocompatibility and biodegradability of metal organic frameworks for biomedical applications

“…35,36 MOFs toxicity depends on several other factors such as the kinetics of degradation, bio-distribution, accumulation in tissues and organs, excretion from the body, applications and balance between risks and benefits and so on. 28,[37][38][39][40][41][42][43][44] MOFs that are used for biomedical applications usually consist of metals that are essential to the body such as iron, zinc and magnesium.…”

“…Furthermore, our group developed a biocompatible and biodegradable immunotherapeutic delivery system using ZIF-8 for the controlled delivery of nivolumab (NV), a monoclonal antibody checkpoint inhibitor (Figure 7). 44 The NV-ZIF has shown a higher efficacy than the naked NV to activate T cells in hematological malignancies. We further modified the system by coating NV-ZIF with breast cancer cell membrane (MCF-7) to enable tumor-specific targeted delivery.…”

Multifunctional Nanocarriers‐Mediated Synergistic Combination of Immune Checkpoint Inhibitor Cancer Immunotherapy and Interventional Oncology Therapy

“…Reproduced with permission. [ 52 ] Copyright 2021, American Association for the Advancement of Science.…”

“…Therefore, NV‐ZIF MCF was delivered to local tumor because of the homing effect of tumor and EPR for sustainable Nivolumab cancer immunotherapy (Figure 4c(iii)). [ 52 ]…”

“…Therefore, NV-ZIF MCF was delivered to local tumor because of the homing effect of tumor and EPR for sustainable Nivolumab cancer immunotherapy (Figure 4c(iii)). [52] These studies utilizing multifunctional nanocarriers offer an effective strategy to combine ICI cancer immunotherapy with other immunogenic therapies in a localized manner. It is evident that nanocarrier-mediated ICI cancer immunotherapy gives potential for enhanced ICI immunotherapies with increased therapeutic dose in the local tumor area.…”