In situ functionalized polymers for siRNA delivery

NOTICE:This is the peer-reviewed version of the following article:Juan M. Priegue, Daniel N. Crisan, José Martínez-Costas, Juan R. Granja, Francisco Fernandez-Trillo, and Javier Montenegro (2016),“In situ Functionalized Polymers for siRNA Delivery ; Angew. Chem. Int. Ed., 55, 7492–7495 [doi: 10.1002/anie.201601441]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for self-archivingA new method is reported herein for screening the biological activity of functional polymers across a consistent degree of polymerization and in situ, that is, under aqueous conditions and without purification/isolation of candidate polymers. In brief, the chemical functionality of a poly(acryloyl hydrazide) scaffold was activated under aqueous conditions using readily available aldehydes to obtain amphiphilic polymers. The transport activity of the resulting polymers can be evaluated in situ using model membranes and living cells without the need for tedious isolation and purification steps. This technology allowed the rapid identification of a supramolecular polymeric vector with excellent efficiency and reproducibility for the delivery of siRNA into human cells (HeLa-EGFP). The reported method constitutes a blueprint for the high-throughput screening and future discovery of new polymeric functional materials with important biological applicationsRoyal Society. Grant Number: IE130688 Spanish Ministry of Economy and Competitiveness. Grant Numbers: CTQ2014-59646-R, CTQ2013-43264-R, BFU2013-43513-R Birmingham Science City European Regional Development Fund Royal Society. Grant Number: RG140273 University of Birmingham MEC MINECO ERC. Grant Number: DYNAP-677786S