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.
ABSTRACT
[This corrects the article DOI: 10.1016/j.bbiosy.2021.100032.].
ABSTRACT
Poly(DL-lactic-co-glycolic acid) and poly(DL-lactic acid) are widely used for the preparation of nanoparticles due to favorable characteristics for medical use like biodegradability and controllable degradation behavior. The contact with different media like human plasma or serum leads to the formation of a protein corona that determines the NP's in vivo processing. In this study, the impact of surface end group identity, matrix polymer hydrophobicity, molecular weight, and incubation medium on the protein corona composition was evaluated. Corona proteins were quantified using Bradford assay, separated by SDS-PAGE, and identified via LC-MS/MS. The acquired data revealed that surface end group identity had the most profound effect on corona composition in both quantitative and qualitative terms. Regarding matrix polymer hydrophobicity, adsorption profiles on NP systems with similar physicochemical characteristics resembled each other. The molecular weight of the matrix polymers proved to impact quantity, but not quality of corona bound proteins. The corona of plasma incubated NP showed adsorption of incubation medium-specific proteins but resembled those of serum incubated NP in terms of protein function, average mass and isoelectric point. Overall, the NP physicochemical properties proved to be easily adjustable determining factors of protein corona formation in physiological environments.
