Acid-labile chemical bonds-based nanoparticles for endosome escape and intracellular delivery
Ruoyu Cheng, Shiqi Wang, Hélder A. Santos
Abstract
In the last years there has been a booming in the development of biological pharmaceuticals, and various nanoparticle delivery systems have been developed to overcome biological barriers to maximize the therapeutic potentials. Especially, when these drug-loaded nanoparticle systems arrive at the target cells, they must be successfully internalized into the cells, followed by the endosome escape, to release the payload in the cytoplasm. This is crucial so that the payloads are not degraded in the endosome (around pH 6.8–6.0) or lysosome (around pH 4.5). Considering the acid environment of the endosome, several studies have shown the design of different acid-labile nanoparticle delivery systems attempting to achieve endosome escape by, for example, endosomal rupture, membrane destabilization, and membrane fusion. In this mini-review, we summarize current designs in acid-labile chemical bonds for endosome escape of nanosystems. First, we briefly introduce the structural design of acid-labile nanoparticles and their endosomal escape mechanisms. Then, we review recent research work on the topic, highlighting how the nanoparticle designs can be used in endosome escape for different biomedical applications. Finally, we discuss the challenges and future perspectives in this field. The potential endosomal escape mechanisms and applications of acid-labile NPs. Upper panel, hydrolysis-induced physicochemical properties variations. Lower panel, endosomolytic moieties release from acid-labile NPs. Right panel, the applications of these acid-labile NPs in tumor treatments, anti-inflammation, and tissue regeneration. Created with BioRender.com .