Investigation of size, surface charge, PEGylation degree and concentration on the cellular uptake of polymer nanoparticles

In this work a large number of polymer nanoparticles (NPs) with different features have been synthesized through emulsion polymerization-based methods. Poly(methyl methacrylate) (PMMA), poly-e{open}-caprolactone (PCL), and poly(lactic acid) (PLA) based NPs with different size, hydrophobicity, surface charge, PEGylation degree, type of emulsifier and ζ potential have been produced and characterized. All the different NPs have been adopted for cellular uptake studies, leading to a precise quantification of the number of internalized NPs into a selected tumor cell line. The experiments summarize, emphasize and improve the comprehension of the influence of NPs features on the uptake efficiency. In detail, a linear relationship between uptake and both size and NP concentration independently upon other NP characteristics was found. Moreover, it was confirmed that cells are able to internalize and retain for a long time preferentially positively charged NPs. Finally, by coupling results of uptake studies with cell viability measurements, an easy and fast check to control the effectiveness of a selected polymer as drug carrier has been proposed. In particular, we observed that biodegradable PLA-based NPs with high molecular weight, non-PEGylated and positively charged PCL NPs are the better choice to maximize the uptake and minimize side effect against cells.