Journal
CHEMISTRY OF MATERIALS
Volume 34, Issue 15, Pages 6868-6882Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.chemmater.2c01168
Keywords
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Funding
- Canadian Institute of Health Research Grants [FDN159932, MOP-1301431]
- Canadian Cancer Society [705285 - 1]
- Canada Research Chairs Program [950 - 223824]
- Nanomedicines Innovation Network [2019-T3-01]
- Graduate Student Endowment Award
- Doctoral Completion Award
- Ontario Graduate Scholarship
- Barbara and Frank Milligan Graduate Fellowship
- Lorne F. Lambier Q.C. Scholarship
- Cecil Yip Award
- Program Completion Award
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Conjugating targeting ligands onto the protein corona of nanoparticles enhances their selectivity for diseased cells and overcomes the negative impact of serum protein adsorption on cellular targeting.
Targeting ligands are conjugated onto nanoparticles to increase their selectivity for diseased cells. However, they become covered by serum proteins which prevent them from binding to target receptors. Here, we show that the nanoparticle protein corona achieved a maximum thickness in serum because the protein adsorption and desorption rates reached an equilibrium. Simulation experiments suggest that the number of molecular interactions between proteins decrease with distance from the nanoparticle surface until the forces are too weak to hold the proteins together. This results in an equilibration state between the proteins on the nanoparticle surface and in biological fluids. Conjugating targeting ligands to this equilibrated protein corona allowed the nanoparticles to bind to target cells in the presence of serum proteins. In contrast, conjugating targeting ligands directly to the nanoparticle surface resulted in a 55% reduction in binding to target cells in serum. We demonstrated this concept using two nanoparticle material types with different surface chemistries. We present a ligand-on-corona conjugation strategy that overcomes the negative impact of serum protein adsorption on nanoparticle cellular targeting.
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