Dynamic covalent polymers (DCPs) recently emerged as smart siRNA delivery vectors, which dynamically self-assemble through siRNA templating and depolymerize in a controlled manner. Herein, we report the dynamic combinatorial screening of cationic and amphiphilic peptide-based monomers. We provide experimental evidence, by mass spectrometry analyses, of the siRNA-templated formation of DCPs, and show that amphiphilic DCPs display superior activity in terms of siRNA complexation and delivery in cells. Thus, the work describes a new type of siRNA vector based on dynamic covalent lipopolyplexes, which feature improved activity as well as better nano-structuration compared to previous generations of DCPs.

This article is Open Access

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