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.
|Number of pages||8|
|Journal||Journal of Controlled Release|
|State||Published - Sep 11 2007|
Bibliographical noteFunding 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.
- Heat shock protein 90
- Intelligent biosynthetic nanobiomaterial (IBN)
- Recombinant block copolymer
- Thermal drug targeting
ASJC Scopus subject areas
- Pharmaceutical Science