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Biophysical Characterization of a Riboflavin-Conjugated Dendrimer Platform for Targeted Drug Delivery

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posted on 13.02.2012 by Amanda B. Witte, Christine M. Timmer, Jeremy J. Gam, Seok Ki Choi, Mark M. Banaszak Holl, Bradford G. Orr, James R. Baker, Kumar Sinniah
The present study describes the biophysical characterization of generation-five poly­(amidoamine) (PAMAM) dendrimers conjugated with riboflavin (RF) as a cancer-targeting platform. Two new series of dendrimers were designed, each presenting the riboflavin ligand attached at a different site (isoalloxazine at N-3 and d-ribose at N-10) and at varying ligand valency. Isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) were used to determine the binding activity for riboflavin binding protein (RfBP) in a cell-free solution. The ITC data shows dendrimer conjugates have KD values of ≥465 nM on a riboflavin basis, an affinity ∼93-fold lower than that of free riboflavin. The N-3 series showed greater binding affinity in comparison with the N-10 series. Notably, the affinity is inversely correlated with ligand valency. These findings are also corroborated by DSC, where greater protein–conjugate stability is achieved with the N-3 series and at lower ligand valency.

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