The Binding Affinities of Serum Proteins to Nanoparticles
Nanoparticles can be coated with targeting ligands to deliver medical agents to specific cells. Serum protein adsorption affects the binding of nanoparticles to target cells. We hypothesized that serum proteins and target receptors compete for binding to nanoparticles. We tested the serum protein binding affinity of 251 nanoparticle designs. Here, we discovered that the binding affinities of serum proteins and receptors to a nanoparticle determine whether it can bind to target cells. We developed and validated a quantitative metric, the binding ratio, to identify nanoparticle designs that can bind to targets in serum with 90% sensitivity and 88% specificity. Using the binding ratio as a numerical guideline for nanoparticle design enabled us to improve the efficiency of nanoparticle binding to target cellular receptors.
Authors
- Guanyou Lin (ORCID: https://orcid.org/0000-0002-1706-5463)
- Benjamin Stordy (ORCID: https://orcid.org/0000-0002-1096-3287)
- Warren C. W. Chan (ORCID: https://orcid.org/0000-0001-5435-4785)
- Colin Blackadar (ORCID: https://orcid.org/0000-0002-3847-3693)
- Neil P. King (ORCID: https://orcid.org/0000-0002-2978-4692)
- Wei Yang (ORCID: https://orcid.org/0000-0002-8979-5967)
- Rashmi Ravichandran (ORCID: https://orcid.org/0000-0002-2630-7487)
- Luis Ricardez‐Sandoval (ORCID: https://orcid.org/0000-0001-9867-6778)
- Derrick R. Hicks (ORCID: https://orcid.org/0000-0003-2950-1848)
- Gabriel D. Patrón (ORCID: https://orcid.org/0000-0001-5241-1416)
- Mikhail G. Shapiro (ORCID: https://orcid.org/0000-0002-0291-4215)
- Anthony J. Tavares
- David A. Baker (ORCID: https://orcid.org/0000-0001-7896-6217)
- Bill Ling (ORCID: https://orcid.org/0000-0002-1276-7204)
- Zahra Sepahi
- Alexander D. Goodson (ORCID: https://orcid.org/0000-0002-5301-3695)
- Ayden Malekjahani
- Miqin Zhang (ORCID: https://orcid.org/0000-0001-8974-1494)
Institutions
- California Institute of Technology (US)
- Howard Hughes Medical Institute (US)
- University of Waterloo (CA)
- Nanyang Technological University (SG)
- University of Toronto (CA)
- University of Washington (US)
- National Institute for Nanotechnology (CA)
- Division of Chemistry (US)
- Institute of Biomedical Science (GB)
- Imperial College London (GB)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-06-09
- DOI
- https://doi.org/10.1021/jacs.5c02576
- Citations
- 5
- Primary Topic
- Nanoparticle-Based Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 2.99
Funders
- Bill and Melinda Gates Foundation
- Kuni Foundation
- National Institutes of Health
- Natural Sciences and Engineering Research Council of Canada