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

Abstract

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.

Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs

“…Protein therapeutics have been intensively explored as new modalities for the treatment of cancer, diabetes, infectious diseases, respiratory diseases, etc. However, many of the currently used protein therapeutics ( e.g ., enzymes, antibodies, and hormones) target secreted or extracellular domains 78 , 79 . Developing the delivery of proteins to target intracellular domains can open up protein-based therapeutics to more applications.…”

Thiol‐Disulfide Exchange as a Route for Endosomal Escape of Polymeric Nanoparticles

“…for therapeutics delivery to mitigate poor stability and cellular uptake of bioactive molecules. [1][2][3][4] The most dominant route of cellular entry for nanoparticles is through endocytosis, where these drug carriers are initially trapped in vesicular endosomes. [5,6] Considering that the therapeutic activity of these molecules occur in the cytosol or other subcellular compartments besides the lysosome, escape of the nanocarriers from the endosome is critical for success for therapies involving intracellular targets.…”

Nanobodies Right in the Middle: Intrabodies as Toolbox to Visualize and Modulate Antigens in the Living Cell

“…To avoid genetic cell manipulation one might try to deliver intrabodies directly as proteins. Multiple methods and technologies for protein transduction are now available (reviewed in [ 35 , 36 , 37 ] with focus on antibodies) which also can be applied for Nbs. Physical methods including electroporation, microinjection, sonoporation or transfer by cell squeezing [ 38 , 39 , 40 ] can be used to transfer Nbs into cells.…”