Facile Synthesis of Multivalent Folate-Block Copolymer Conjugates via Aqueous RAFT Polymerization: Targeted Delivery of siRNA and Subsequent Gene Suppression
Document Type
Article
Publication Date
4-1-2009
Department
Chemistry and Biochemistry
School
Mathematics and Natural Sciences
Abstract
Cell specific delivery of small interfering ribonucleic acid (siRNA) using well-defined multivalent folate-conjugated block copolymers is reported. Primary amine functional, biocompatible, hydrophilic-block-cationic copolymers were synthesized via aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization. N-(2-hydroxypropyl)methacrylamide) (HPMA), a permanently hydrophilic monomer, was copolymerized with a primary amine containing monomer, N-(3-aminopropyl)methacrylamide (APMA). Poly(HPMA) confers biocompatibility, while APMA provides amine functionality, allowing conjugation of folate derivatives. HPMA-stat-APMA was chain extended with a cationic block, poly(N-[3-(dimethylamino)propyl]methacrylamide), to promote electrostatic complexation between the copolymer and the negatively charged phosphate backbone of siRNA. Notably, poly(HPMA) stabilizes the neutral complexes in aqueous solution, while APMA allows the conjugation of a targeting moiety, thus, dually circumventing problems associated with the delivery of genes via cationically charged complexes (universal transfection). Fluorescence microscopy and gene down-regulation studies indicate that these neutral complexes can be specifically delivered to cancer cells that overexpress folate receptors.
Publication Title
Biomacromolecules
Volume
10
Issue
4
First Page
936
Last Page
943
Recommended Citation
York, A. W.,
Zhang, Y.,
Holley, A. C.,
Guo, Y.,
Huang, F.,
McCormick, C. L.
(2009). Facile Synthesis of Multivalent Folate-Block Copolymer Conjugates via Aqueous RAFT Polymerization: Targeted Delivery of siRNA and Subsequent Gene Suppression. Biomacromolecules, 10(4), 936-943.
Available at: https://aquila.usm.edu/fac_pubs/8940