Naslov
Targeting a c-Myc Inhibitory Polypeptide to Specific Intracellular Compartments using Cell Penetrating Peptides

Autori
Bidwell, Gene L. 3rd ; Davis, Aisha N. ; Raucher, Dražen

Izvornik
Journal of controlled release (0168-3659) 135 (2009), 1; 2-10

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

Ključne riječi
elastin-like polypeptide; c-Myc; thermal targeting; cell penetrating peptide; subcellular localization

Sažetak
The therapeutic index of current anti-cancer chemotherapeutics can be improved by two major mechanisms: 1) developing drugs which are specifically toxic to the cancer cells and 2) developing methods to deliver drugs to the tumor site. In an attempt to combine these approaches, we developed a thermally responsive polypeptide inhibitor of c-Myc. This polypeptide is based on the thermally responsive Elastin-like polypeptide (ELP). When injected systemically, ELP-fused drugs will aggregate and accumulate at the tumor site where local hyperthermia is applied. ELP was fused to a peptide which blocks c-Myc/Max dimerization (H1), thereby inhibiting transcription activation by c-Myc (ELP-H1). In this study, the cellular uptake, intracellular distribution, and potency of the Pen, Tat and Bac cell penetrating peptides fused to ELP-H1 were evaluated. While Pen-ELP-H1 and Tat-ELP-H1 were localized in the cytoplasm, Bac-ELP-H1 localized to the nucleus in a subset of the cells and was the most potent inhibitor of MCF-7 cell proliferation. This data demonstrates that ELP can be targeted to the desired cellular compartment simply by choice of the CPP used, resulting in a more potent nuclear targeted c-Myc inhibitory polypeptide which may be beneficial in cancer therapy.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA