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

详细信息    查看全文

• 作者：Amanda B. Witte ; Christine M. Timmer ; Jeremy J. Gam ; Seok Ki Choi ; Mark M. Banaszak Holl ; Bradford G. Orr ; James R. Baker ; Jr. ; Kumar Sinniah
• 刊名：Biomacromolecules
• 出版年：2012
• 出版时间：February 13, 2012
• 年：2012
• 卷：13
• 期：2
• 页码：507-516
• 全文大小：464K
• 年卷期：v.13,no.2(February 13, 2012)
• ISSN：1526-4602

文摘

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 K_D values of 鈮?65 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鈥揷onjugate stability is achieved with the N-3 series and at lower ligand valency.