Mechanisms of cellular uptake of nanoparticles and their effect on drug delivery

Abstract

In the field of diagnosis and treatment in contemporary medicine, nanoparticles (NPs) are an important novelty. They are drug delivery systems on the nanometer scale, whose uptake mechanisms and routes of internalization differ, depending on their properties. For successful treatment, it is crucially important to understand the interplay between uptake mechanisms and NP properties. In this article mechanisms of NP uptake and the subsequent intracellular events are presented. NPs can enter cells via phagocytotic or non-phagocytotic pathways (clathrin-mediated endocytosis, caveolae- mediated endocytosis, macropinocytosis, other endocytotic pathways). The route of internalization determines the site of drug release, which can be in the acidic and enzyme rich environment of lysosomes, or NPs avoid this compartment and release drug in the cytosol or another organelle. This process can be controlled by a careful selection of NP ingredients and precise design of their physico-chemical properties (size, shape, surface properties). Phagocytosis is generally undesirable, since its main purpose is the elimination of foreign materials from the body, and therefore the drug taken up in this way is usually lost. To avoid this internalization mechanism, the particles should be small showing a hydrophilic surface. However, the most successful approach is to attach ligands to the NP surface, which governs the uptake through non-phagocytotic mechanisms. Knowledge about cellular uptake mechanisms is crucial for predicting drug delivery to the target site in the cell, since it can lead to better stability of NPs and preserved biological activity of labile drugs.