Endoprotease-mediated intracellular protein delivery using nanocapsules

Anuradha Biswas, Kye Il Joo, Jing Liu, Muxun Zhao, Guoping Fan, Pin Wang, Zhen Gu, Yi Tang

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Proteins possess distinct intracellular roles allowing them to have vast therapeutic applications. However, due to poor cellular permeability and fragility of most proteins, intracellular delivery of native, active proteins is challenging. We describe a biomimetic protein delivery vehicle which is degradable upon the digestion by furin, a ubiquitous intracellular protease, to release encapsulated cargos. Proteins were encapsulated in a nanosized matrix prepared with monomers and a bisacrylated peptide cross-linker which can be specifically recognized and cleaved by furin. Release of encapsulated protein was confirmed in a cell-free system upon proteolytic degradation of nanocapsules. In vitro cell culture studies demonstrated successful intracellular delivery of both nuclear and cytosolic proteins and confirmed the importance of furin-degradable construction for native protein release. This endoprotease-mediated intracellular delivery system may be extended to effectively deliver various biological therapeutics.

Original languageEnglish
Pages (from-to)1385-1394
Number of pages10
JournalACS Nano
Volume5
Issue number2
DOIs
StatePublished - 22 Feb 2011

Keywords

  • endoprotease
  • intracellular
  • nanocapsule
  • polymer
  • protein delivery

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