Targeted delivery of siRNA using glycopolymer

Liver is an essential part of the human biological system as it serves to detoxify, synthesize protein and produce biochemicals necessary for digestion. However, there have been common liver diseases namely, hepatitis (A, B, C, and E), fatty liver, cirrhosis and ultimately liver cancer. RNA interference (RNAi) mediated through double-stranded small interfering RNA (siRNA) pave the way to knockdown disease causing gene.1 Nevertheless, effective delivery of siRNA is an arduous task as they are very prone to degradation and are difficult to target specific cells. Glycopolymers are carbohydrates based polymers that recognise biological receptors on cells.2 This project focuses on the design of synthetic glycopolymer architectures using reversible addition-fragmentation transfer (RAFT) polymerization of sugar containing monomers for conjugations of siRNA. Galactose based monomer are selected here, as liver cancer cells over-expressed asialoglycoproteins, which are galactose recognising receptors. Moreover, synthetic delivery system has been reported to protect enzymatic degradation of therapeutics during delivery in the biological enviroment.3 Figure 1 shows the synthetic approach towards glycopolymers for the conjugation of siRNA by using a 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid (CPDT) RAFT agent, 4,4′-Azobis(4-cyanovaleric acid) (ACVA) initiator polymerized in dioxane. Figure 2 display the increased in molecular weights of polymers with increasing monomer conversions