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Pregled bibliografske jedinice broj: 507985

A thermally targeted elastin-like polypeptide-doxorubicin conjugate overcomes drug resistance

Bidwell, G.L.; Davis, A.N.; Fokt, I.; Priebe, W.; Raucher, Dražen
A thermally targeted elastin-like polypeptide-doxorubicin conjugate overcomes drug resistance // Investigational new drugs, 25 (2007), 4; 313-326 doi:10.1007/s10637-007-9053-8 (međunarodna recenzija, članak, znanstveni)

A thermally targeted elastin-like polypeptide-doxorubicin conjugate overcomes drug resistance

Bidwell, G.L. ; Davis, A.N. ; Fokt, I. ; Priebe, W. ; Raucher, Dražen

Investigational new drugs (0167-6997) 25 (2007), 4; 313-326

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

Ključne riječi
Drug delivery; thermal targeting; drug resistance

The ability of cancer cells to become simultaneously resistant to different drugs, a trait known as multidrug resistance, remains a major obstacle for successful anticancer therapy. One major mechanism of resistance involves cellular drug efflux by expression of P-glycoprotein (P-gp), a membrane transporter with a wide variety of substrates. Anthracyclines are especially prone to induction of resistance by the P-gp mechanism. P-gp mediated resistance is often confronted by use of P-gp inhibitors, synthesis of novel analogs, or conjugating drugs to macromolecular carriers in order to circumvent the efflux mechanism. In this report, the effect of free and Elastin-like polypeptide (ELP) bound doxorubicin (Dox) on the viability of sensitive (MES-SA and MCF-7) and multidrug resistant (MES-SA/Dx5 and NCI/ADR-RES) human carcinoma cells was studied in vitro. The resistant MES-SA/Dx5 cells demonstrated about 70 times higher resistance to free Dox than the sensitive MES-SA cells, and the NCI/ADR-RES cells were about 30 fold more resistant than the MCF-7 cells. However, the ELP-bound Dox was equally cytotoxic in both sensitive and resistant cell lines. The ELP-bound Dox was shown to accumulate in MES-SA/Dx5 cells, as opposed to free Dox, which was rapidly pumped out by the P-gp transporter. Since ELP is a thermally responsive carrier, the effect of hyperthermia on the cytotoxicity of the ELP-Dox conjugate was investigated. Both cytotoxicity and apoptosis were enhanced by hyperthermia in the Dox resistant cells. The results suggest that ELP-Dox conjugates may provide a means to thermally target solid tumors and to overcome drug resistance in cancer cells

Izvorni jezik

Znanstvena područja
Biologija, Temeljne medicinske znanosti


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

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

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