Thermally Targeted Delivery of a C-Myc Inhibitory Peptide to Breast Tumors in Vivo Using Elastin-Like Polypeptide (CROSBI ID 581450)
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Podaci o odgovornosti
Raucher, Dražen ; Bidwell III, Gene L ; Perkins, Eddie
engleski
Thermally Targeted Delivery of a C-Myc Inhibitory Peptide to Breast Tumors in Vivo Using Elastin-Like Polypeptide
Although surgical resection with adjuvant chemotherapy and/or radiotherapy are used to treat breast tumors, normal tissue tolerance, development of metastases, and inherent tumor resistance to radiation or chemotherapy can hinder a successful outcome. Therefore, it is necessary to consider alternative targeted therapeutic approaches for adjuvant therapy that would significantly reduce undesired side effects in normal tissues. We have developed a thermally responsive polypeptide (CPP-ELP-H1) that inhibits breast cancer cell proliferation by blocking the activity of the oncogenic protein c-Myc. When administered IV into mice bearing orthotopic, syngeneic breast tumors, CPP-ELP-H1 exhibited a long plasma half life and accumulated in tumor tissue. The tumor levels of the CPP-ELP delivered H1 peptide were enhanced when hyperthermia was applied to the tumor site. Daily administration (7 days) of CPP-ELP-H1 followed by tumor heating induced over 70% reduction in tumor volume compared to unheated controls or controls lacking the H1 inhibitory peptide. This work provides a new modality for targeted delivery of a specific oncogene inhibitor. In addition to the peptide’s intrinsic tumor targeting due to its oncogene inhibition, ELP can be physically targeted to the tumor site by application of external hyperthermia. Specific targeting of the proposed therapeutic polypeptides by local hyperthermia to breast tumors or to areas of potential metastasis following tumor resection would increase specificity and efficacy of treatment and reduce the cytotoxicity in normal tissues
Targeted drug delivery; c-Myc; Peptides; Hyperthermia
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Podaci o prilogu
2011.
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objavljeno
Podaci o matičnoj publikaciji
1538-7445
Podaci o skupu
102nd Annual Meeting of the American Association for Cancer Research
poster
02.04.2011-06.04.2011
Orlando (FL), Sjedinjene Američke Države