Synthesis of a family of amphiphilic glycopolymers via controlled ring-opening polymerization of functionalized cyclic carbonates and their application in drug delivery.
Polymers bearing pendant carbohydrates have a variety of biomedical applications especially in the area of targeted drug delivery. Here we report the synthesis of a family of amphiphilic block glycopolymers containing d glucose, d galactose and d mannose via metal-free organocatalyzed ring-opening polymerization of functional cyclic carbonates generating narrowly dispersed products of controlled molecular weight and end-group fidelity, and their application in drug delivery. These glycopolymers self-assemble into micelles having a high density of sugar molecules in the shell, a size less than 100 nm with narrow size distribution even after drug loading, and little cytotoxicity, which are important for drug delivery. Using galactose-containing micelles as an example, we demonstrate their strong targeting ability towards ASGP-R positive HepG2 liver cancer cells in comparison with ASGP-R negative HEK293 cells although the galactose is attached to the carbonate monomer at 6-position. The enhanced uptake of DOX-loaded galactose-containing micelles by HepG2 cells significantly increases cytotoxicity of DOX as compared to HEK293. This new family of amphiphilic block glycopolymers has great potential as carriers for targeted drug delivery.
Suriano
Fabian
F
Center of Innovation and Research in Materials and Polymers (CIRMAP), Laboratory of Polymeric and Composite Materials, University of Mons, Mons, Belgium.
Pratt
Russell
R
Tan
Jeremy P K
JP
Wiradharma
Nikken
N
Nelson
Alshakim
A
Yang
Yi-Yan
YY
Dubois
Philippe
P
Hedrick
James L
JL
D001212:Asialoglycoproteins / Q000494:pharmacology; D002241:Carbohydrates / Q000138:chemical synthesis* / Q000737:chemistry; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003500:Cyclization / Q000187:drug effects; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D016503:Drug Delivery Systems; D060748:Fetuins; D005453:Fluorescence; D005690:Galactose / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011076:Polycarboxylate Cement / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D013696:Temperature; D000509:alpha-Fetoproteins / Q000494:pharmacology
D001212:Asialoglycoproteins; D002241:Carbohydrates; D060748:Fetuins; D008823:Micelles; D011076:Polycarboxylate Cement; D011108:Polymers; D000509:alpha-Fetoproteins; C017029:asialofetuin; C005506:polycarbonate; D004317:Doxorubicin; D005947:Glucose; D005690:Galactose