Journal
POLYMER CHEMISTRY
Volume 2, Issue 7, Pages 1428-1441Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c1py00038a
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Funding
- National Science Foundation [DR-0213883]
- NSF [EPS-0903787]
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The advent of controlled radical polymerization (CRP) techniques, along with advancements in facile conjugation chemistry, now allow synthetic tailoring of precise, polymeric architectures necessary for drug/gene delivery. Reversible addition-fragmentation chain transfer (RAFT) polymerization and its aqueous counterpart (aRAFT) afford quantitative control over key synthetic parameters including block length, microstructure, and placement of structo-pendent and structo-terminal functionality for conjugation of active agents and targeting moieties. The relevance of water-soluble and amphiphilic (co) polymers synthesized by RAFT for in vivo delivery of therapeutics in biological fluids is an especially attractive feature. In many cases, polymerization, binding, conjugation, and stimulus-induced release can be accomplished directly in aqueous media. This review focuses on RAFT synthesized (co) polymers as vectors for delivery of small interfering ribonucleic acid (siRNA) and gene down-regulation via the RNA interference (RNAi) pathway. Synthetic strategies utilizing RAFT and facile side-and end-chain reaction chemistries to afford modular delivery architectures (linear, stars/hyperbranched, micelles, and hybrid (co) polymeric vehicles) are reviewed based on examples from current literature. Also, specific problems, barriers, and challenges regarding rational design of polymeric delivery systems for therapeutic siRNA are presented.
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