Folate-conjugated thermoresponsive block copolymers: highly efficient conjugation and solution self-assembly.
A combination of controlled radical polymerization and azide-alkyne click chemistry was employed to prepare temperature-responsive block copolymer micelles conjugated with biological ligands with potential for active targeting of cancer tissues. Block copolymers of N-isopropylacrylamide (NIPAM) and N,N-dimethylacrylamide (DMA) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization with an azido chain transfer agent (CTA). Pseudo-first-order kinetics and linear molecular weight dependence on conversion were observed for the RAFT polymerizations. CuI-catalyzed coupling with propargyl folate resulted in folic acid residues being efficiently conjugated to the alpha-azido chain ends of the homo and block copolymers. Temperature-induced self-assembly resulted in aggregates capable of controlled release of a model hydrophobic drug. CuI-catalyzed azide-alkyne cycloaddition has proven superior to conventional methods for conjugation of biological ligands to macromolecules, and the general strategy presented herein can potentially be extended to the preparation of folate-functionalized assemblies with other stimuli susceptibility (e.g., pH) for therapeutic and imaging applications.
De
Priyadarsi
P
Department of Chemistry, Southern Methodist University, 3215 Daniel Avenue, Dallas, Texas 75275-0314, USA.
Gondi
Sudershan R
SR
Sumerlin
Brent S
BS
D000178:Acrylamides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001386:Azides / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry*; D006358:Hot Temperature; D006801:Humans; D008024:Ligands; D008823:Micelles; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D012996:Solutions
D000178:Acrylamides; D000970:Antineoplastic Agents; D001386:Azides; D003692:Delayed-Action Preparations; D008024:Ligands; D008823:Micelles; D011108:Polymers; D012996:Solutions; D003300:Copper; D005492:Folic Acid; C099046:N,N-dimethylacrylamide; C067295:N-isopropylacrylamide