Amphiphilic block copolymer conjugated with cell-penetrating-peptides derived from Influenza A H1N1 virus as a biocompatible scaffold for enhanced cell-uptake

Amphiphilic copolymers prepared by reversible addition-fragmentation chain-transfer (RAFT) polymerization are versatile and biocompatible scaffolds for multiple drug delivery applications. Decorating these structures with biomolecules and targeting moieties is a proven approach to enhance the cell uptake of polymers. In particular, spike proteins on the surface of the influenza A H1N1 virus are biomacromolecules highly evolved to promote cell adhesion and uptake, leading to effective cell-penetrating processes. We harnessed this uptake ability by selecting the peptide sequences responsible for the cell uptake and grafting them on a methacrylate copolymer. The adopted polymeric scaffold included glycerol, butyl, and N-hydroxy succinimide ester (NHS- ester) groups. This polymer resulted in a water-dispersible and biocompatible structure. Moreover, the reactivity of NHS-ester units enabled the modular insertion of the peptide in post-polymerization reactions. Through this approach, we combined the cell penetration efficiency of influenza A H1N1 virus with the easy manipulation of polymers and small biomolecules. The resulting bioconjugate was demonstrated to be a modular, safe, and effective platform for potential intracellular delivery applications.