Subtle changes to polymer structure and degradation mechanism enable highly effective nanoparticles for siRNA and DNA delivery to human brain cancer.

ABSTRACT: Polymeric materials can be used to deliver nucleic acids such as DNA plasmids and siRNA, but often have low efficacy in human cells. To improve gene delivery, an array of over 70 hydrolytically degradable and bioreducible poly(beta-amino ester)s are synthesized and the properties of over 200 nanoparticle formulations fabricated from these biomaterials are evaluated. The effect of different polymer structures on the delivery of nucleic acids of different structures and sizes, including siRNA, linear DNA, and circular DNAs (1.8-26 kb), is evaluated. Significantly, leading hydrolytically degradable polymeric nanoparticles deliver DNA to 90 ± 2% of primary human glioblastoma cells with <10% nonspecific cytotoxicity, better than leading commercially available reagents (p < 0.01). Bioreducible p

SUBMITTER: Tzeng SY 

PROVIDER: S-EPMC3838886 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature