PEGylated and zwitterated silica nanoparticles as doxorubicin carriers applied in a breast cancer cell line: Effects on protein corona formation

Nanomaterials exposed to biological fluids form protein coronas on their surfaces, changing their original properties. Surface functionalization with nonfouling moieties is a strategy to synthesize silica nanoparticles (SiNPs) with the ability to hinder protein corona formation. We report a simple poly(ethylene glycol) (PEG) and zwitterionic (ZWT)-based surface modification method to prepare doxorubicin-loaded SiNPs to avoid protein corona formation in breast cancer cells. Drug-loaded SiNPs were characterized in terms of particle size, charge, and drug loading content. A comparison of the stability between PEG and ZWT on SiNP surfaces was performed at 25 °C and 37 °C in a high salt solution using turbidimetry. At 37 °C, the PEGylated SiNPs showed aggregation. In contrast, under the same conditions, zwitterated SiNPs did not show aggregation. Both PEG and ZWTSiNP savoided protein adsorption in the presence of increasing concentrations of bovine serum albumin (BSA). In vitro cell experiments demonstrated that both functionalization approaches (SiNPs-PEG and SiNPs-ZWT) improved biocompatibility in the breast cancer cell line MCF-7compared to SiNPs. The antitumour effects of doxorubicin-loaded SiNPs were evaluated via red neutral cell uptake and annexin V assays, and the results demonstrated that surface functionalization plays an important role in the cytotoxic profile of these systems, with SiNPs-DOX-PEG and SiNPs-DOX-ZWT exhibiting a superior cytotoxic effect compared to SiNPs-DOX.