Design, Synthesis, and Biological Functionality of a Dendrimer-Based Modular Drug Delivery Platform

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• 作者：Douglas G. Mullen ; Daniel Q. McNerny ; Ankur Desai ; Xue-min Cheng ; Stassi C. DiMaggio ; Alina Kotlyar ; Yueyang Zhong ; Suyang Qin ; Christopher V. Kelly ; Thommey P. Thomas ; Istvan Majoros ; Bradford G. Orr ; James R. Baker ; Jr. ; Mark M. Banaszak Holl
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：April 20, 2011
• 年：2011
• 卷：22
• 期：4
• 页码：679-689
• 全文大小：1054K
• 年卷期：v.22,no.4(April 20, 2011)
• ISSN：1520-4812

文摘

A modular dendrimer-based drug delivery platform was designed to improve upon existing limitations in single dendrimer systems. Using this modular strategy, a biologically active platform containing receptor mediated targeting and fluorescence imaging modules was synthesized by coupling a folic acid (FA) conjugated dendrimer with a fluorescein isothiocyanate (FITC) conjugated dendrimer. The two different dendrimer modules were coupled via the 1,3-dipolar cycloaddition reaction (鈥渃lick鈥?chemistry) between an alkyne moiety on the surface of the first dendrimer and an azide moiety on the second dendrimer. Two simplified model systems were also synthesized to develop appropriate 鈥渃lick鈥?reaction conditions and aid in spectroscopic assignments. Conjugates were characterized by ¹H NMR spectroscopy and NOESY. The FA-FITC modular platform was evaluated in vitro with a human epithelial cancer cell line (KB) and found to specifically target the overexpressed folic acid receptor.