Targeted drug delivery system inspired by macropinocytosis

Macropinocytosis is a widely-observed and evolutionarily-conserved endocytic process found in the eukaryotic cells. In comparison to other endocytic routes, macropinocytosis allows for the internalization of greater quantities of fluid-phase drugs, making it an attractive avenue for drug delivery. Recent evidence showed that various drug delivery systems can be internalized through macropinocytosis. Utilizing macropinocytosis may therefore provide a new avenue for targeted intracellular delivery. In this review, we provide an overview into the origins and distinctive properties of macropinocytosis, summarize the roles of macropinocytosis under healthy and pathological settings. Furthermore, we highlight the biomimetic and synthetic drug delivery systems that employ macropinocytosis as the primary internalization mechanism. To facilitate the clinical applications of these drug delivery systems, additional research can be conducted to enhance the cell-type selectivity of macropinocytosis, the control of drug release at the target, and the prevention of potential toxicity. The rapidly emerging field of macropinocytosis-based targeted drug delivery and therapies holds great potential to drastically increase the efficiency and specificity of drug delivery. We present the role of macropinocytosis in both physiological and pathological processes and highlight the biomimetic and synthetic drug delivery systems that utilize macropinocytosis as the internalization mechanism. [Display omitted] •We review the origin and features of macropinocytosis, and its functions under healthy and pathological settings.•We highlight biomimetic and synthetic drug delivery systems that employ macropinocytosis as the internalization mechanism.•We discuss the potential development and clinical application for macropinocytosis-based drug delivery systems.