Intracellular Delivery: An Overview

Targeted intracellular delivery is gaining importance, especially for improved therapy of cancer and intracellular infections. Endocytosis or cellular internalization, a physiological process for intracellular delivery of nutrients or destruction of pathogens, involves two major pathways, namely phagocytosis or cell eating, which enable uptake of solid particles and pinocytosis or cell drinking. Pinocytosis includes fluid-phase endocytosis (macropinocytosis/micropinocytosis) and receptor-mediated endocytosis (RME). While phagocytosis, macropinocytosis, and micropinocytosis are nonselective, RME is a selective process of internalization, which is triggered by association of the receptor with specific ligands. Among endocytic processes, phagocytosis and RME are relied on for nanocarrier-based targeted drug delivery. This chapter describes various pathways with emphasis on phagocytosis and strategies to bypass lysosomal destruction of drugs. A major focus, however, is RME with a detailed discussion on clathrin, caveolin, and clathrin- and caveolin-independent pathways, and also provides a list of receptors based on the internalization pathway. Targeted delivery of drugs to subcellular organelles is also discussed. The discussion on the impact of nanocarrier properties on cellular internalization of nanocarriers throws light on factors to be addressed during nanoparticle design. This chapter thereby enables a comprehensive understanding of intracellular uptake in the context of targeted drug delivery.