Binding affinity and kinetic analysis of targeted small molecule-modified nanoparticles
Duffner, Jay L.
Lewis, Timothy A.
Schreiber, Stuart L.
Koehler, Angela N.
Shaw, Stanley Y.
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CitationTassa, Carlos, Jay L. Duffner, Timothy A. Lewis, Ralph Weissleder, Stuart L. Schreiber, Angela N. Koehler, and Stanley Y. Shaw. 2010. “Binding Affinity and Kinetic Analysis of Targeted Small Molecule-Modified Nanoparticles.” Bioconjugate Chemistry 21 (1): 14–19. https://doi.org/10.1021/bc900438a.
AbstractNanoparticles bearing surface-conjugated targeting ligands are increasingly being explored for it variety of biomedical applications. The multivalent conjugation of targeting ligands on the surface of nanoparticles is presumed to enhance binding to the desired target. However, given the complexities inherent in the interactions of nanoparticle surfaces with proteins, and the Structural diversity of nanoparticle scaffolds and targeting ligands, Our understanding of flow conjugation of targeting ligands affects nanoparticle binding remains incomplete. Here, we use surface plasmon resonance (SPR) to directly and quantitatively study the affinity and binding kinetics of nanoparticles that display small molecules conjugated to their surface. We studied the interaction between I single protein target and it Structurally related series of targeting ligands whose intrinsic affinity varies over a 4500-fold range and performed SPR at protein densities that reflect endogenous receptor densities. We report that even weak small molecule targeting ligands can significantly enhance target-specific avidity (by up to 4 orders of magnitude) through multivalent interactions and also observe it Much broader range of kinetic effects than has been previously reported. Quantitative measurement of how the affinity and kinetics of nanoparticle binding vary as a function of different surface conjugations is a rapid, generalizable approach to nanoparticle characterization that can inform the design of nanoparticles for biomedical applications.
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