Recent progress in nanomedicine-mediated cytosolic delivery.

Cytosolic delivery of bioactive agents has exhibited great potential to cure undruggable targets and diseases. Because biological cell membranes are a natural barrier for living cells, efficient delivery methods are required to transfer bioactive and therapeutic agents into the cytosol. Various strategies that do not require cell invasive and harmful processes, such as endosomal escape, cell-penetrating peptides, stimuli-sensitive delivery, and fusogenic liposomes, have been developed for cytosolic delivery. Nanoparticles can easily display functionalization ligands on their surfaces, enabling many bio-applications for cytosolic delivery of various cargo, including genes, proteins, and small-molecule drugs. Cytosolic delivery uses nanoparticle-based delivery systems to avoid degradation of proteins and keep the functionality of other bioactive molecules, and functionalization of nanoparticle-based delivery vehicles imparts a specific targeting ability. With these advantages, nanomedicines have been used for organelle-specific tagging, vaccine delivery for enhanced immunotherapy, and intracellular delivery of proteins and genes. Optimization of the size, surface charges, specific targeting ability, and composition of nanoparticles is needed for various cargos and target cells. Toxicity issues with the nanoparticle material must be managed to enable clinical use.