Glucose-functionalized, serum-stable polymeric micelles from the combination of anionic and RAFT polymerizations

Ligeng Yin, Molly C. Dalsin, Antons Sizovs, Theresa M. Reineke, Marc A. Hillmyer

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Poly(ethylene-alt-propylene)-poly[(N,N-dimethylacrylamide) -grad-(2-methacrylamido glucopyranose)] (PEP-poly(DMA-grad-MAG), or PG) diblock terpolymers were synthesized by combining anionic and reversible addition-fragmentation chain transfer (RAFT) polymerizations. An ω-trithiocarbonate-functionalized PEP homopolymer served as the macromolecular chain transfer agent (macroCTA), and RAFT copolymerizations of DMA and a trimethylsilyl-protected MAG (TMS-MAG) monomer gave a family of PG diblock terpolymers after hydrolysis. The terpolymers had similar degrees of polymerization, and the MAG content ranged from 3.5 to 39 mol % in the hydrophilic block. At 70°C, the reactivity ratios of DMA (1) and TMS-MAG (2) were determined to be r 1 = 1.86 ± 0.07 and r 2 = 0.16 ± 0.01, and thus the poly(meth)acrylamide blocks in the PG diblock terpolymers were likely to be gradient copolymers. Micellar dispersions from PG diblock polymers in water were examined by cryogenic transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS). Spherical micelles with core radii of ca. 7 nm and overall hydrodynamic radii of ca. 15 nm were the predominant morphologies observed in all samples prepared by sequential nanoprecipitation and dialysis. The electron-dense MAG moieties greatly increased the native contrast of the micellar coronae, which were clearly viewed as gray halos around the micellar cores in samples with relatively large MAG content. The stability of the glucose-installed micelles was tested in four biologically relevant media, from simple phosphate-buffered saline (PBS) to fetal bovine serum (FBS), using a combination of DLS and cryo-TEM measurements. Micellar dispersions from a PG diblock terpolymer with 16 mol % of MAG of the hydrophilic block were stable in 100% FBS over at least 14 h, suggesting their minimal interactions with serum proteins. Control experiments suggested that micelles composed of PDMA alone in the corona had similar serum stabilities. These sugar-functionalized micelles hold promise as in vivo drug delivery vehicles to possibly prolong circulation time after intravenous administration.

Original languageEnglish (US)
Pages (from-to)4322-4332
Number of pages11
Issue number10
StatePublished - May 22 2012


Dive into the research topics of 'Glucose-functionalized, serum-stable polymeric micelles from the combination of anionic and RAFT polymerizations'. Together they form a unique fingerprint.

Cite this