Combinatorial polymer and lipidoid libraries for nanomedicine

Combinatorial biomaterial libraries were created to advance genetic nanomedicine. An initial library of 2350 cationic poly(beta-amino ester)s was synthesized and screened using high-throughput techniques to find polymers effective for gene delivery. This library was then combinatorially modified to create next-generation polymers with advanced drug delivery functionality. Polymer structure was correlated to gene delivery function. A library of 1200 cationic lipoids was also synthesized and screened using high-throughput techniques. This library was optimized for the delivery of siRNA and oligoRNA and novel lipid-like compounds were discovered that were highly efficacious. Lead polymers have efficacy comparable to adenovirus for gene delivery in vitro and, with cytotoxic DNA payloads, can induce tumor regression in vivo. Lead lipidoids can provide for effective siRNA delivery in a number of cell types and animal models, including non-human primates.