Biodegradable nanoparticles bearing amine groups as a strategy to alter surface features, biological identity and accumulation in a lung metastasis model

Polymer-based nanoparticles (NPs) with a cationic charge have been emerged recently as a potent nanotool due to their unique ability to penetrate deeply inside tumor tissue and to interact preferentially with plasma membrane of cancer cells. In this paper, we propose a general strategy to obtain biodegradable cationic NPs of poly(?-caprolactone) (PCL) based on an amine terminated PCL (NH2-PCL4.2k) or its mixture with monomethoxypoly(ethylenglycol)-PCL (mPEG1k-PCL4k). Positively-charged NPs were obtained, switching to net negative values through adsorption of low molecular weight hyaluronan (HA). NPs exposing both amine and PEG groups on the surface showed a larger Fixed Aqueous Layer Thickness as compared to fully PEGylated NPs, suggesting that PEG conformation/localization is affected by the presence of aminic groups. Stability positively-charged NPs was affected by the presence of ions, while interaction with human plasma protein pool indicated a time-dependent protein corona formation imparting an overall negative charge. NPs hemolysis was low while cytotoxicity against A549 and Calu-3 lung cancer cell lines was cell-specific as well as dose and time-dependent. Finally, the presence of amine groups greatly changed in vivo biodistribution of NPs in tumor-bearing mice (lung colonization of B16F10 cancer cells) allowing aminic/PEGylated NPs to accumulate mainly at target organ. Overall, this study demonstrates that NPs with a mixed aminic/PEGylated surface show peculiar biological identity that alters their interaction in the bioenvironment and thus worth of further investigation in chemotherapeutic delivery.