The benefcial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate.Moreover,the dynamic nature of plasma membrane accounts for the movem...The benefcial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate.Moreover,the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only infuencing their pharmacokinetic and pharmacodynamic properties but also bioavailability,therapeutic effcacy and toxicity.Therefore,an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential.In order to direct nanoparticles towards specifc sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated.These include particle size,shape and surface charge/chemistry.Restricting the particle size of nanocarriers below 200 nm contributes to internalization via clathrin and caveolae mediated pathways.Similarly,a moderate negative surface potential confers endolysosomal escape and targeting towards mitochondria,endoplasmic reticulum(ER)and Golgi.This review aims to provide an insight into these physicochemical attributes of nanocarriers fabricated using amphiphilic graft copolymers affecting cellular internalization.Fundamental principles understood from experimental studies have been extrapolated to draw a general conclusion for the designing of optimized nanoparticulate drug delivery systems and enhanced intracellular uptake via specifc endocytic pathway.展开更多
基金financially sponsored by extramural research funding support from Department of Science and Technology,Rajasthan(Project#P.7(3)Wipro/R&D/2016/6009,India)。
文摘The benefcial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate.Moreover,the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only infuencing their pharmacokinetic and pharmacodynamic properties but also bioavailability,therapeutic effcacy and toxicity.Therefore,an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential.In order to direct nanoparticles towards specifc sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated.These include particle size,shape and surface charge/chemistry.Restricting the particle size of nanocarriers below 200 nm contributes to internalization via clathrin and caveolae mediated pathways.Similarly,a moderate negative surface potential confers endolysosomal escape and targeting towards mitochondria,endoplasmic reticulum(ER)and Golgi.This review aims to provide an insight into these physicochemical attributes of nanocarriers fabricated using amphiphilic graft copolymers affecting cellular internalization.Fundamental principles understood from experimental studies have been extrapolated to draw a general conclusion for the designing of optimized nanoparticulate drug delivery systems and enhanced intracellular uptake via specifc endocytic pathway.
