Intelligent biosynthetic nanobiomaterials for hyperthermic combination chemotherapy and thermal drug targeting of HSP90 inhibitor geldanamycin

Younsoo Bae, Rita A. Buresh, Tracy P. Williamson, Tze Haw Howard Chen, Darin Y. Furgeson

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

An intelligent biosynthetic nanobiomaterial (IBN) platform was explored for drug delivery applications for hyperthermic combination chemotherapy and thermal drug targeting. Geldanamycin (GA), a heat shock protein 90 inhibitor, was conjugated to novel thermosensitive poly(K)8-poly(VPGXG)60 block copolymers [K8-ELP(1-60)] with guest residues as valine, alanine and glycine in a 5:2:3 ratio at the 'X' position. The conjugates were completely soluble in PBS and showed a characteristic thermosensitive inverse phase transition. [K8-ELP(1-60)]-GA conjugate nanoparticles showed a size ranging from 50 to 200 nm depending upon temperature. Relevant to systemic drug delivery in vivo, these IBNs stably disperse in aqueous solution. Cytotoxicity assays have shown that the IBN from [K8-ELP(1-60)]-GA conjugates exhibits effective hyperthermic combination chemotherapy with facile heat modulation.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
JournalJournal of Controlled Release
Volume122
Issue number1
DOIs
StatePublished - Sep 11 2007

Bibliographical note

Funding Information:
We thank Prof. Ashutosh Chilkoti (Duke University) for kindly providing the ELP(1-30) gene and Prof. Glen Kwon (University of Wisconsin-Madison) for use of the NICOMP DLS. This work was funded by University of Wisconsin-Madison start-up funds to DYF. This work was graciously supported by the 2007 PhRMA Foundation Research Starter Grant awarded to DYF.

Keywords

  • Geldanamycin
  • Heat shock protein 90
  • Hyperthermia
  • Intelligent biosynthetic nanobiomaterial (IBN)
  • Recombinant block copolymer
  • Thermal drug targeting

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'Intelligent biosynthetic nanobiomaterials for hyperthermic combination chemotherapy and thermal drug targeting of HSP90 inhibitor geldanamycin'. Together they form a unique fingerprint.

Cite this