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Well-defined water-soluble block copolymers poly(ethylene glycol)-b-poly(N-(2-hydroxypropyl) methacrylamide-co-N-methacryloylglycylglycine) (PEG-b-P(HPMA-co-MAGG)) and their doxorubicin (Dox) conjugates with different composition and molecular weight were synthesized. These Dox conjugates can form micelles in buffer solution. The physicochemical properties, in vivo biodistribution, blood clearance, and especially the tumor accumulation of copolymers and micelles were studied. Severe liver accumulation can be observed for PEG-b-PMAGG copolymers. This was quite different from their Dox conjugate for which decreased RES uptake and elevated kidney accumulation could be observed. When decrease the negative charge to an appropriate amount such as 8-10 mol %, both RES uptake and kidney accumulation could be suppressed. Obvious tumor accumulation could be achieved especially when the molecular weight were increased from ∼40 to ∼80 KDa. These results provided us with a guideline for the design of nanoscaled drug delivery system as well as a potential option for treating kidney-related cancers.

Soluble hyperbranched glycopolymers were prepared by copolymerization of glycan monomers with reversible addition-fragmentation chain transfer polymerization (RAFT) inimers in a simple one-pot reaction. Two novel RAFT inimers, 2-(methacryloyloxy)ethyl 4-cyano-4-(phenylcarbonothioylthio) pentanoate (MAE-CPP) and 2-(3-(benzylthiocarbonothioylthio) propanoyloxy)ethyl acrylate (BCP-EA) were synthesized and used to prepare hyperbranched glycopolymers. Two types of galactose-based saccharide monomers,, containing a methacrylate and an acrylamide group, respectively, were also synthesized and polymerized under the mediation of the MAE-CPP and BCP-EA inimers, respectively. In addition, hyperbranched poly (proGal-M), linear poly(proGal-A), and hyperbranched poly(pro-Gal-A) were generated and their polymerization kinetics were studied and compared. An unexpected difference was observed in the kinetics between the two monomers during polymerization: the relationship between polymerization rate and concentration of inimer was totally opposite in the two monomer-inimer systems. Branching analysis was conducted by using degree of branching (DB) as the measurement parameter. As expected, a higher DB occurred with increased inimer content. Furthermore, these polymers were readily deprotected by hydrolysis in trifluoroacetic acid solution resulting in watersoluble polymers. The resulting branched glycopolymers have potential as biomimetics of polysaccharides.

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