Lineage of lipid-based endosomal escape in cytosolic delivery to cancer: insight into an unprecedented approach

Endosomal sequestration of lipid-based systems constitutes a significant limitation that undermines the efficient intracellular delivery of therapeutics in cancer treatment. Upon administration, the intracellular fate of drug or gene constructs within lipid-based delivery systems is influenced by various factors, including p-glycoprotein-mediated efflux and lysosomal degradation, which impede sufficient therapeutic agents from reaching their intended targets. This review exhaustively discusses lipids (properties of lipids and role of pKa) and various lipid-based delivery systems facilitating the endosomal escape for cancer treatment. All aspects, such as endosomal sequestration, methods to promote endosomal escape, a mechanistic overview of endosomal escape, detection of endosomal escape, the application potential of lipid-based systems for cancer treatment, and safety of lipid-based systems, were covered in this manuscript. Existing reviews on endosomal escape have accounted for the various mechanisms,. Still, this review paper also furnishes the role of pKa and applications of molecular dynamic simulation in lipid-based drug delivery, and safety concernsof lipid-based nanosystems. This review discussed the influence of material properties on the endosomal escape of therapeutic agents.