Nanoparticle–Cell Interactions: Surface Chemistry Effects on the Cellular Uptake of Biocompatible Block Copolymer Assemblies

The development of nanovehicles for intracellular drug delivery is strongly bound to the understating and control of nanoparticles cellular uptake process, which in turn is governed by surface chemistry. In this study, we explored the synthesis, characterization, and cellular uptake of block copolymer assemblies consisting of a pH-responsive poly­[2-(diisopropyl­amino)­ethyl methacrylate] (PDPA) core stabilized by three different biocompatible hydrophilic shells (a zwitterionic type poly­(2-methacryl­oyloxyethyl phosphorylcholine) (PMPC) layer, a highly hydrated poly­(ethylene oxide) (PEO) layer with stealth effect, and an also proven nontoxic and nonimmunogenic poly­(N-(2-hydroxypropyl)­methacrylamide) (PHPMA) layer). All particles had a spherical core–shell structure. The largest particles with the thickest hydrophilic stabilizing shell obtained from PMPC40-b-PDPA70 were internalized to a higher level than those smaller in size and stabilized by PEO or PHPMA and produced from PEO122-b-PDPA43 or PHPMA64-b-PDPA72, respectively. Such a behavior was confirmed among different cell lines, with assemblies being internalized to a higher degree in cancer (HeLa) as compared to healthy (Telo-RF) cells. This fact was mainly attributed to the stronger binding of PMPC to cell membranes. Therefore, cellular uptake of nanoparticles at the sub-100 nm size range may be chiefly governed by the chemical nature of the stabilizing layer rather than particles size and/or shell thickness.