Intracellular Antibody Delivery Mediated by Lipids, Polymers, and Inorganic Nanomaterials for Therapeutic Applications

Therapeutic antibodies, due to their high affinity and specificity toward their biological targets, may demonstrate reduced harmful side effects compared with traditional drug moieties. While most of the as‐yet clinically approved antibody therapeutics have targeted extracellular or membrane‐bound domains, the ability to target intracellular antigens with antibodies opens up tremendous opportunities for imaging, diagnosis, and therapeutic applications. Generally, delivery concerns have limited the ability to target intracellular antigens, as many antibodies cannot easily cross the cell membrane due to their size and surface chemistry. Delivery platforms have been explored to address this issue, including physical methods, fusion protein/peptide techniques, and synthetic carrier‐based systems. This review summarizes the progress of carrier‐based intracellular antibody delivery systems employing synthetic lipids, polymers, and inorganic nanomaterials. Antibodies targeting various epitopes have been loaded through adsorption, conjugation, or physical encapsulation strategies. Successful intracellular deliveries have been demonstrated largely through fluorescence imaging using dye‐labeled antibody cargos. Specific synthetic delivery platforms have great potential for ex vivo and in vivo therapeutic applications. Challenges and opportunities are further discussed for material scientists to explore in this research area.