Chemoselective ligation in the functionalization of polysaccharide-based particles.
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.
Beaudette
Tristan T
TT
Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Cohen
Joel A
JA
Bachelder
Eric M
EM
Broaders
Kyle E
KE
Cohen
Jessica L
JL
Engleman
Edgar G
EG
Fréchet
Jean M J
JM
D000080:Acetals / Q000737:chemistry; D000818:Animals; D002417:Cattle; D003911:Dextrans / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity; D013499:Surface Properties
D000080:Acetals; D003911:Dextrans; D004337:Drug Carriers; D011134:Polysaccharides