The Binding Affinities of Serum Proteins to Nanoparticles

Benjamin P. Stordy; Zahra Sepahi; Gabriel D. Patrón; Wei Yang; Alexander D. Goodson; Colin Blackadar; Anthony J. Tavares; Guanyou Lin; Ayden Malekjahani; Bill Ling; Rashmi Ravichandran; Derrick R. Hicks; Mikhail G. Shapiro; Miqin Zhang; Neil P. King; David Baker; Luis A. Ricardez-Sandoval; Warren C.W. Chan

doi:10.1021/jacs.5c02576

The Binding Affinities of Serum Proteins to Nanoparticles

Benjamin P. Stordy, Zahra Sepahi, Gabriel D. Patrón, Wei Yang, Alexander D. Goodson, Colin Blackadar, Anthony J. Tavares, Guanyou Lin, Ayden Malekjahani, Bill Ling, Rashmi Ravichandran, Derrick R. Hicks, Mikhail G. Shapiro, Miqin Zhang, Neil P. King, David Baker, Luis A. Ricardez-Sandoval, Warren C.W. Chan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Journal	Journal of the American Chemical Society
DOIs	https://doi.org/10.1021/jacs.5c02576
Publication status	Accepted/In press - 2025
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2025 American Chemical Society.

ASJC Scopus Subject Areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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10.1021/jacs.5c02576

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Stordy, B. P., Sepahi, Z., Patrón, G. D., Yang, W., Goodson, A. D., Blackadar, C., Tavares, A. J., Lin, G., Malekjahani, A., Ling, B., Ravichandran, R., Hicks, D. R., Shapiro, M. G., Zhang, M., King, N. P., Baker, D., Ricardez-Sandoval, L. A., & Chan, W. C. W. (Accepted/In press). The Binding Affinities of Serum Proteins to Nanoparticles. Journal of the American Chemical Society. https://doi.org/10.1021/jacs.5c02576

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title = "The Binding Affinities of Serum Proteins to Nanoparticles",

abstract = "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.",

author = "Stordy, {Benjamin P.} and Zahra Sepahi and Patr{\'o}n, {Gabriel D.} and Wei Yang and Goodson, {Alexander D.} and Colin Blackadar and Tavares, {Anthony J.} and Guanyou Lin and Ayden Malekjahani and Bill Ling and Rashmi Ravichandran and Hicks, {Derrick R.} and Shapiro, {Mikhail G.} and Miqin Zhang and King, {Neil P.} and David Baker and Ricardez-Sandoval, {Luis A.} and Chan, {Warren C.W.}",

note = "Publisher Copyright: {\textcopyright} 2025 American Chemical Society.",

year = "2025",

doi = "10.1021/jacs.5c02576",

language = "English",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

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T1 - The Binding Affinities of Serum Proteins to Nanoparticles

AU - Stordy, Benjamin P.

AU - Sepahi, Zahra

AU - Patrón, Gabriel D.

AU - Yang, Wei

AU - Goodson, Alexander D.

AU - Blackadar, Colin

AU - Tavares, Anthony J.

AU - Lin, Guanyou

AU - Malekjahani, Ayden

AU - Ling, Bill

AU - Ravichandran, Rashmi

AU - Hicks, Derrick R.

AU - Shapiro, Mikhail G.

AU - Zhang, Miqin

AU - King, Neil P.

AU - Baker, David

AU - Ricardez-Sandoval, Luis A.

AU - Chan, Warren C.W.

PY - 2025

Y1 - 2025

N2 - 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.

AB - 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.

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JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

ER -

The Binding Affinities of Serum Proteins to Nanoparticles

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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