Tuning the protein corona of PLGA nanoparticles: Characterization of trastuzumab adsorption behavior and its cellular interaction with breast cancer cell lines

The protein corona (PC) that forms around nanoparticles (NPs) upon exposure to biological media can “mask” targeting ligands that have been attached covalently or adsorptively to the NP surface, potentially decreasing targeting efficiency. In this study, NPs composed of the biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) were incubated with human serum albumin (HSA) as a model protein and trastuzumab as a functional antibody and consequently tested for their interaction with HER2/neu receptor-expressing cell lines. Adsorption behavior was investigated in the presence of competing human plasma (HP) and serum (HS) to determine whether trastuzumab remains adsorptively bound in the PC or “masking” and even displacement effects are to be expected. By fluorescence quantification and LC-MS/MS measurements, trastuzumab could be classified as “hard corona” protein, while HSA appeared as a “soft corona” protein. It was shown that while undirected cell uptake occurred upon exposition to HSA-incubated NPs, through the adsorptive decoration with trastuzumab, HER2/neu receptor-expressing breast cancer cell lines can be selectively addressed.