Chemoselective Ligation in the Functionalization of Polysaccharide-Based Particles

• Published in: Journal of the American Chemical Society 2009-08, Vol.131 (30), p.10360-10361
• Main Authors: Beaudette, Tristan T, Cohen, Joel A, Bachelder, Eric M, Broaders, Kyle E, Cohen, Jessica L, Engleman, Edgar G, Fréchet, Jean M. J
• Format: Article
• Language: English
• Subjects: Acetals - chemistry; Animals; Cattle; Dextrans - chemistry; Dextrans - metabolism; Drug Carriers - chemistry; Drug Carriers - metabolism; HeLa Cells; Humans; Nanoparticles - chemistry; Polysaccharides - chemistry; Polysaccharides - metabolism; Substrate Specificity; Surface Properties
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja903984s

Despite the promise of precisely targeted or otherwise functionalized polymeric particulate drug delivery vehicles, typical biocompatible particles are generally not amenable to facile and selective surface modification. Herein, we report the development of a simple, mild, and chemoselective strategy for the conjugation of biologically active molecules to the surface of dextran-based microparticles. Alkoxyamine-bearing reagents were used to form stable oxime conjugates with latent aldehyde functionality present in reducing carbohydrate chain ends. We demonstrate the functionalization of dextran-based microparticles with a fluorophore as well as a cell-penetrating peptide sequence, which facilitated the delivery of cargo to nonphagocytic cells leading to a 60-fold increase in the expression of a reporter gene when plasmid DNA-loaded particles were used.