Amphiphilic block polymers consist of covalently-bonded hydrophobic and hydrophilic polymer segments. Akin to small molecule amphiphiles, these macromolecules self-assemble into a variety of well-defined structures in aqueous solution such as micelles and vesicles. However, the macromolecular nature of the hydrophobic block can lead to very slow and seemingly nonexistent micelle dynamics. This kinetic entrapment is an attractive advantage of amphiphilic block polymers for therapeutic agent delivery applications; however, it also leads to path-dependent assembly and unknown (or uncontrollable) longer-term stability. Consequently, careful optimization of the macromolecules is necessary to produce uniform, stable, and responsive macromolecular solution assemblies. One area of interest in our research group is exploring the ability to externally control the delivery of nucleic acids to various cellular targets using copolymer nanocontainers. In this area, we are designing and synthesizing new cationic diblock copolymers containing PEG and <i>o</i>-nitrobenzyl moieties that facilitate both tailorable nucleic acid complexation and light-activated release. Our design unlocks a new approach to advance non-viral gene therapy by overcoming the dual constraints of tight extracellular packaging and facile intracellular decomplexation. Through this modular micelle approach, we are able to significantly enhance nucleic acid uptake and gene silencing efficiency.

Manipulating solution-assembled and stimuli-responsive copolymer nanostructures for nucleic acid delivery and gene silencing

250th National Meeting (2015)

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