Barth, Christina, et al. “Spacer length and serum protein adsorption affect active targeting of trastuzumab-modified nanoparticles.” Biomaterials and Biosystems 5 (2022): 100032. https://doi.org/10.1016/j.bbiosy.2021.100032

Abstract

Receptor-mediated active targeting of nanocarriers is a widely investigated approach to specifically address cancerous cells and tissues in the human body. The idea is to use these formulations as drug carriers with enhanced specificity and therefore reduced systemic side effects. Until today a big obstacle to reach this goal remains the adsorption of serum proteins to the nanocarrier’s surface after contact with biological fluids. In this context different nanoparticle characteristics could be beneficial for effective active targeting after formation of a protein corona which need to be identified. In this study trastuzumab was used as an active targeting ligand which was covalently attached to human serum albumin nanoparticles. For coupling reaction different molecular weight spacers were used and resulting physicochemical nanoparticle characteristics were evaluated. The in vitro cell association of the different nanoparticle formulations was tested in cell culture experiments with or without fetal bovine serum. For specific receptor-mediated cell interaction SK-BR-3 breast cancer cells with human epidermal growth factor receptor 2 (HER2) overexpression were used. MCF-7 breast cancer cells with normal HER2 expression served as control. Furthermore, serum protein adsorption on respective nanoparticles was characterized. The qualitative and quantitative composition of the protein corona was analyzed by SDS-PAGE and LC-MS/MS and the influence of protein adsorption on active targeting capability was determined.