Packaging plasmid DNA into virus-mimicking micelles with tunable shape and size
Despite advances over the past two decades in nanoparticle-mediated delivery, poor nanoparticle stability and inefficient intracellular delivery remains a major roadblock in targeted delivery through intravascular delivery. We have developed engineering approaches to control the self-assembly process for plasmid DNA (Jiang, et al, 2010; 2011; 2012; 2013; Qu, et al, 2015) or siRNA (Shyam, et al, 2015) with cationic polymers to form micellar nanoparticles that allow control over the size, shape, surface properties, colloidal stability, and complex stability of the nanoparticles with regulated release of the payload. DNA nanoparticle shape can be tuned from spherical and toroidal to rod-like, and to worm-like morphology with size in 20 – 100 nm range (Jiang, et al, 2013). Through a combined experimental and computational approach in collaboration with Prof. Erik Luijten at Northwestern University, we provided insights in the mechanism in shape regulation during the process. These studies provide guidance to further exploration of shape-controlling factors for DNA-compacting nanoparticles. This shape-controlled micellar design method was recently extended to graft copolymers (Qu, et al, 2015) and siRNA assembly (Shyam, et al, 2015). This polyelectrolyte nanoparticle platform offers an opportunity to investigate the shape-dependent transport and delivery efficiency of virus-mimicking nanoparticles.
Jiang X, Zheng Y, Chen HH, Leong KW, Wang TH, Mao HQ. (2010). Dual-sensitive micellar nanoparticles regulate DNA unpacking and enhance gene-delivery efficiency. Adv. Mater. 22(23): 2556-2560. PMID: 20440698; PMCID: PMC3000804.
Jiang X, Qu W, Pan D, Ren Y, Williford JM, Cui H, Luijten E, Mao HQ. (2013). Plasmid-templated shape control of condensed DNA-block copolymer nanoparticles. Adv. Mater. 25(2): 227-232. PMID: 23055399; PMCID: PMC3918481.
Shyam R, Ren Y, Lee J, Braunstein KE, Mao HQ, Wong PC. (2015). Intraventricular delivery of siRNA nanoparticles to the central nervous system. Mol. Ther. Nucleic Acids. 4: e242. PMID: 25965552.