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

doi:10.1016/j.jconrel.2007.06.005

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

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

26 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 language	English
Pages (from-to)	16-23
Number of pages	8
Journal	Journal of Controlled Release
Volume	122
Issue number	1
DOIs	https://doi.org/10.1016/j.jconrel.2007.06.005
State	Published - 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

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10.1016/j.jconrel.2007.06.005

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title = "Intelligent biosynthetic nanobiomaterials for hyperthermic combination chemotherapy and thermal drug targeting of HSP90 inhibitor geldanamycin",

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.",

keywords = "Geldanamycin, Heat shock protein 90, Hyperthermia, Intelligent biosynthetic nanobiomaterial (IBN), Recombinant block copolymer, Thermal drug targeting",

author = "Younsoo Bae and Buresh, {Rita A.} and Williamson, {Tracy P.} and Chen, {Tze Haw Howard} and Furgeson, {Darin Y.}",

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.",

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AU - Buresh, Rita A.

AU - Williamson, Tracy P.

AU - Chen, Tze Haw Howard

AU - Furgeson, Darin Y.

N1 - 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.

PY - 2007/9/11

Y1 - 2007/9/11

N2 - 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.

AB - 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.

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KW - Thermal drug targeting

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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