PEG-SS-PPS: Reduction-sensitive disulfide block copolymer vesicles for intracellular drug delivery

Simona Cerritelli, Diana Velluto, Jeffrey A. Hubbell

Research output: Contribution to journalArticlepeer-review

344 Scopus citations

Abstract

Under appropriate conditions, block copolymeric macroamphiphiles will self-assemble in water to form vesicles, referred to as polymersomes. We report here polymersomes that can protect biomolecules in the extracellular environment, are taken up by endocytosis, and then suddenly burst within the early endosome, releasing their contents prior to exposure to the harsh conditions encountered after lysosomal fusion. Specifically, block copolymers of the hydrophile poly(ethylene glycol) (PEG) and the hydrophobe poly(propylene sulfide) (PPS) were synthesized with an intervening disulfide, PEG17-SS-PPS30. Polymersomes formed from this block copolymer were demonstrated to disrupt in the presence of intracellular concentrations of cysteine. In cellular experiments, uptake, disruption, and release were observed within 10 min of exposure to cells, well within the time frame of the early endosome of endolysosomal processing. This system may be useful in cytoplasmic delivery of biomolecular drugs such as peptides, proteins, oligonucleotides, and DNA.

Original languageEnglish (US)
Pages (from-to)1966-1972
Number of pages7
JournalBiomacromolecules
Volume8
Issue number6
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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