Intelligent biosynthetic nanobiomaterials for hyperthermic combination chemotherapy and thermal drug targeting of HSP90 inhibitor geldanamycin.
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 [K(8)-ELP(1-60)]-GA conjugates exhibits effective hyperthermic combination chemotherapy with facile heat modulation.
Bae
Younsoo
Y
Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705-2222, USA.
Buresh
Rita A
RA
Williamson
Tracy P
TP
Chen
Tze-Haw Howard
TH
Furgeson
Darin Y
DY
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D016227:Benzoquinones / Q000008:administration & dosage / Q000737:chemistry*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000628:therapy; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004274:DNA, Recombinant / Q000737:chemistry; D016503:Drug Delivery Systems; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D047029:Lactams, Macrocyclic / Q000008:administration & dosage / Q000737:chemistry*; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry*; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D004274:DNA, Recombinant; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D010455:Peptides; D011994:Recombinant Proteins; C001277:geldanamycin