Magnetic nanostructures, Endosomal escape, Proton sponge effect, Membrane destabilization, Membrane translocation, Photochemical, Materials of engineering and construction. Mechanics of materials, TA401-492

Several evolving therapies depend on the delivery of therapeutic cargo into the cytoplasm. Engineered magnetic nanoparticles (MNPs) have played a pivotal role in advancing and modernizing cancer theranostics, vaccination and gene therapies. The main advantages of MNP-based delivery approaches are due to their potential to decrease the side effects by targeting specific cell types, shielding delicate therapeutics from early degradation, increasing the solubility of hard-to-deliver drugs and long-sustained and precise release of these drugs. Like other nanoparticles (NPs), MNPs enter cells by endocytosis and are frequently stuck inside endocytic vesicles, which mature into early and late endosomes and accumulate in the lysosome. Endocytosed MNPs are ultimately degraded in lysosomes or recycled towards the cell membrane. Thereby, they must escape endocytic vesicles on a priority basis. Endosomal escape is highly important for the effectiveness of nanoparticle-based treatments. This review is concerned with the use of magnetic nanoparticles (MNPs) as functional nano-objects to enhance the therapeutic effects by disrupting or rupturing the endocytic vesicles in terms of endosomal escape. The current strategies and future challenges concerning an efficient endosomal escape of MNPs are discussed in this review.