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

被引:24
作者
Bae, Younsoo
Buresh, Rita A.
Williamson, Tracy P.
Chen, Tze-Haw Howard
Furgeson, Darin Y. [1 ]
机构
[1] Univ Wisconsin, Sch Pharm, Div Pharmaceut Sci, Madison, WI 53705 USA
[2] Univ Wisconsin, Dept Biomed Engn, Madison, WI 53705 USA
关键词
intelligent biosynthetic nanobiomaterial (IBN); recombinant block copolymer; thermal drug targeting; heat shock protein 90; geldanamycin; hyperthermia; ELASTIN-LIKE POLYPEPTIDE; SOLID TUMORS; DELIVERY; CONJUGATE; GENE; ACCUMULATION; EXPRESSION; MECHANISM; POLYMERS; MEDICINE;
D O I
10.1016/j.jconrel.2007.06.005
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 [K-8-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. [K-8-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. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:16 / 23
页数:8
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