Redox-responsive nanocapsules for intracellular protein delivery

Muxun Zhao, Anuradha Biswas, Biliang Hu, Kye Il Joo, Pin Wang, Zhen Gu, Yi Tang

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

Abstract

Direct delivery of proteins to the cytosol of cells holds tremendous potential in biological and medical applications. Engineering vehicles for escorting proteins to the cytosol in a controlled release fashion has thus generated considerable interest. We report here the preparation of redox-responsive single-protein nanocapsules for intracellular protein delivery. Through in situ interfacial polymerization, the target protein is noncovalently encapsulated into a positively-charged polymeric shell interconnected by disulfide-containing crosslinkers. The dissociation of the polymeric shell under reducing conditions and the subsequent release of protein were confirmed using cell-free assays in the presence of glutathione (GSH). The nanocapsules were demonstrated to be efficiently internalized into the cells and to release the protein in the reducing cytosol. Using the nanocapsule as a vehicle, we showed that active caspase 3 (CP-3) can be delivered and can induce apoptosis in a variety of human cancer cell lines, including HeLa, MCF-7 and U-87 MG. Our approach therefore presents an effective intracellular protein delivery strategy for therapeutic, diagnostic and reprogramming applications.

Original languageEnglish
Pages (from-to)5223-5230
Number of pages8
JournalBiomaterials
Volume32
Issue number22
DOIs
StatePublished - Aug 2011

Keywords

  • Apoptosis
  • Degradable material
  • Disulfide
  • Endocytosis
  • Nanogels

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