Effectively delivering a unique Hsp90 inhibitor using star polymers

Seong Jong Kim, Deborah M. Ramsey, Cyrille Boyer, Thomas P. Davis, Shelli R. McAlpine

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Abstract

We report the synthesis of a novel heat shock protein 90 (hsp90) inhibitor conjugated to a star polymer. Using reversible addition-fragmentation chain-transfer (RAFT) polymerization, we prepared star polymers comprising PEG attached to a predesigned functional core. The stars were cross-linked using disulfide linkers, and a tagged version of our hsp90 inhibitor was conjugated to the polymer core to generate nanoparticles (14 nm). Dynamic light scattering showed that the nanoparticles were stable in cell growth media for 5 days, and high-performance liquid chromatography (HPLC) analysis of compound-release at 3 different pH values showed that release was pH dependent. Cell cytotoxicity studies and confocal microscopy verify that our hsp90 inhibitor was delivered to cells using this nanoparticle delivery system. Further, delivery of our hsp90 inhibitor using star polymer induces apoptosis by a caspase 3-dependent pathway. These studies show that we can deliver our hsp90 inhibitor effectively using star polymers and induce apoptosis by the same pathway as the parent compound.

Original languageEnglish
Pages (from-to)915-920
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume4
Issue number10
DOIs
Publication statusPublished - 10 Oct 2013
Externally publishedYes

Keywords

  • cyclic peptides
  • drug delivery
  • drug-peptide conjugation
  • Heat shock protein 90
  • hsp90
  • macrocycles
  • nanoparticles
  • polymers
  • star polymer

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