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Pregled bibliografske jedinice broj: 507913

A thermally responsive biopolymer conjugated to an acid-sensitive derivative of paclitaxel stabilizes microtubules, arrests cell cycle, and induces apoptosis


Moktan, Shama; Ryppa, Claudia; Kratz, Felix; Raucher, Dražen
A thermally responsive biopolymer conjugated to an acid-sensitive derivative of paclitaxel stabilizes microtubules, arrests cell cycle, and induces apoptosis // INVESTIGATIONAL NEW DRUGS, 30 (2012), 1; 236-248 doi:10.1007/s10637-010-9560-x (međunarodna recenzija, članak, znanstveni)


Naslov
A thermally responsive biopolymer conjugated to an acid-sensitive derivative of paclitaxel stabilizes microtubules, arrests cell cycle, and induces apoptosis

Autori
Moktan, Shama ; Ryppa, Claudia ; Kratz, Felix ; Raucher, Dražen

Izvornik
INVESTIGATIONAL NEW DRUGS (0167-6997) 30 (2012), 1; 236-248

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Paclitaxel; thermal targeting

Sažetak
Poor aqueous solubility limits the therapeutic index of paclitaxel as an anti-cancer drug. Synthesis of soluble prodrugs of paclitaxel, or conjugation of the drug to macromolecular carriers have been reported to increase its water-solubility. Macromolecular drug carriers have an added advantage of targeting the drug to the tumor site due to the abnormal tumor blood and lymphatic vasculature. This study describes a thermally responsive macromolecular carrier, elastin-like polypeptide (ELP) for the delivery of paclitaxel. Paclitaxel was bound to ELP by conjugation with the 6-maleimidocaproyl hydrazone derivative of paclitaxel, an acid-sensitive paclitaxel prodrug, for the potential treatment of breast cancer. Focused hyperthermia above a specific transition temperature at the site of a tumor causes ELP to aggregate and accumulate, thereby increasing the local concentration of the drug cargo. The paclitaxel prodrug described here bears an acid-sensitive linker that is cleavable at the lysosomal/endosomal pH, which allows a controlled intracellular release of the drug. The ELP-delivered paclitaxel in the presence of hyperthermia inhibits MCF-7 cell proliferation by stabilizing the microtubule structures, arresting the cells at the G2/M stage, and inducing apoptosis in a manner similar to conventional paclitaxel. It also inhibits proliferation of a paclitaxel resistant MCF-7 cell line. These data provide an in vitro proof of concept for the use of ELP as a delivery vehicle of paclitaxel.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
219-0000000-3364 - Ciljano toplinsko dopremanje lijekova u solidne tumore (Dražen Raucher, )

Ustanove
Medicinski fakultet, Osijek

Autor s matičnim brojem:
Dražen Raucher, (280455)

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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