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• W2026166688 abstract "Peptide based therapy is a promising field of anti-cancer therapy. The biologically active therapeutic peptides, derived from an endogenous protein or designed synthetically, can inhibit or activate important cellular pathways to promote cancer cell death. The major challenges of peptide based therapy are stability and tumor-specificity of the therapeutic peptides. One of the methods to increase stability and target the therapeutic peptide to the tumor site is to utilize stimulus-responsive macromolecular carriers. We have designed a therapeutic peptide, SynB1-ELP-(KLAKLAK) 2 based on the thermally responsive biopolymer, elastin-like polypeptide (ELP) and the mitochondrial membrane disrupting proapoptotic peptide, (KLAKLAK) 2 . Additionally, a cell penetrating peptide, SynB1 has been included in the N-terminus of this polypeptide in order to increase the polypeptide9s membrane permeability. SynB1 is an 18-mer peptide derived from protegrins, which are antimicrobial peptides found in porcine leukocytes. The utilities of ELP are two-fold - 1) it is a macromolecule and therefore can provide stability to the overall polypeptide system, and 2) it is thermally responsive and therefore can be targeted to the tumor site by external application of local hyperthermia. The unique phase transition property of ELP allows it to remain soluble at physiological temperature but forces it to aggregate in response to mild hyperthermia (40 - 42 °C). Therefore, SynB1-ELP-(KLAKLAK) 2 can be targeted to solid tumors by the application of local hyperthermia without being degraded before reaching the tumor. The anti-proliferative effect of SynB1-ELP-(KLAKLAK) 2 was examined in MCF-7 breast cancer cells. While the polypeptide was not cytotoxic to cells at 37 °C, it killed about 40% of cells at 42 °C after 6 days with two one hour treatments. Similar treatment schedule resulted in approximately 4-fold increase in apoptosis induction at 42 °C compared to 37 °C. Confocal microscopy showed that SynB1-ELP-(KLAKLAK) 2 localizes in the mitochondria which supports the mitochondrial membrane disrupting feature of the (KLAKLAK) 2 peptide. In conclusion, SynB1-ELP-(KLAKLAK) 2 localizes in the mitochondria and inhibits the proliferation of MCF-7 cells in combination with hyperthermia by inducing apoptosis. Further studies include determining the proapoptotic effects of SynB1-ELP-(KLAKLAK) 2 in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5520." @default.
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• W2026166688 date "2010-04-15" @default.
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• W2026166688 title "Abstract 5520: Thermally targeted proapoptotic peptide for cancer therapy" @default.
• W2026166688 doi "https://doi.org/10.1158/1538-7445.am10-5520" @default.
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