Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers

• Published in: Acta pharmaceutica Sinica. B Vol. 11; no. 4; pp. 903 - 924
• Main Authors: Mazumdar, Samrat, Chitkara, Deepak, Mittal, Anupama
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2021; Elsevier
• Subjects: Amphiphilic; Copolymer; Internalization; Intracellular fate; Nanoparticles; Review; Intracellular fate; Cav-1; RES; Amphiphilic; Rmin; SR & LR; IL-2; RBITC; DOX; ER; HER-2; Nanoparticles; AR; CCP; FITC; Rmax; Internalization; Cy; mPEG; SEM; Copolymer; TEM; Rmin, maximum size threshold value; RES, reticuloendothelial system; RBITC, rhodamine B isothiocyanate; Rmax, minimum size threshold value; DOX, doxorubicin; FITC, fluorescein isothiocyanate; Cav-1, caveolin-1; TEM, transmission electron microscopy; HER-2, human epidermal growth factor receptor 2; SR & LR, short rod and long rod; IL-2, interleukin; Cy, cyanine; CCP, clathrin coated pits; SEM, scanning electron microscopy; AR, aspect ratio; ER, endoplasmic reticulum; mPEG, methoxy poly(ethylene glycol)
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2021.02.019

The beneficial 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 influencing their pharmacokinetic and pharmacodynamic properties but also bioavailability, therapeutic efficacy and toxicity. Therefore, an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential. In order to direct nanoparticles towards specific 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 specific endocytic pathway. Understanding the parameters controlling nanocarrier endocytosis and intracellular fate is essential to predict their pharmacokinetic and pharmacodynamic behavior. Directing nanoparticles towards specific sub-cellular organelles requires the manipulation of physicochemical attributes. [Display omitted]