Polymerization-Induced Electrostatic Self-Assembly Enables Noncytotoxic Polyplex Formation for Gene Delivery

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Abstract
Gene delivery is a cornerstone of both basic research and gene therapy, where it holds the key to treating genetic disorders at their source. However, it does not adhere to one-size-fits-all solutions. Cargo-tailored and time-saving approaches are urgently needed for different applications. Photoinduced electron/energy transfer reversible addition-fragmentation chain-transfer (PET-RAFT) polymerization is a technique that enables the synthesis of a wide range of well-defined polymers, allowing for rapid reaction condition screening in small volumes. In this work, polymerization-induced electrostatic self-assembly (PIESA) based on PET-RAFT polymerization is demonstrated to facilitate the simultaneous synthesis and assembly of pDNA polyplexes for transfection. The as-prepared polyplexes are shown to be less cytotoxic than their conventionally assembled counterparts and act as more effective gene delivery vehicles in transfection trials. This strategy provides a versatile platform that facilitates rapid screening of cell-compatible copolymer nanoparticle compositions for gene delivery in ultralow volumes.
Funding Information
  • Engineering and Physical Sciences Research Council (EP/P025021/1)
  • Engineering and Physical Sciences Research Council (EP/P025498/1)
  • Engineering and Physical Sciences Research Council (EP/R00661X/1)
  • Engineering and Physical Sciences Research Council (EP/S019367/1)
  • Engineering and Physical Sciences Research Council (EP/W024-497/2)
  • Engineering and Physical Sciences Research Council (EP/W524347/1)
  • European Regional Development Fund (OC15R19P)

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