Internalizing therapeutic molecules or genes into cells and safely delivering them to the target tissue where they can perform the intended tasks is one of the key characteristics of the smart gene/drug delivery vector. Despite much research in this field, endosomal escape continues to be a significant obstacle to the development of effective gene/drug delivery systems. In this review, we discuss in depth the several types of endocytic pathways involved in the endolysosomal trapping of therapeutic agents. In addition, we describe numerous mechanisms involved in nanoparticle endosomal escape. Furthermore, many other techniques are employed to increase endosomal escape to minimize entrapment of therapeutic compounds within endolysosomes, which have been reviewed at length in this study.
Keywords: endocytic pathways; endolysosomal degradation of therapeutics; endolysosomal trapping; mechanism of endosomal escape; strategies for enhancing endosomal escape.
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