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- W2003860897 abstract "Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FLDoxorubicin is an anthracycline used in the treatment of many types of cancer. It intercalates into the strands of DNA to inhibit the progression of topoisomerase II, stopping the cell from replicating. The side effects, however, are severe and include neutropenia, alopecia, nausea, myelosuppression, and cardiotoxicity. Due to its nonspecific effect, high doses are needed to treat cancer cells. These high doses are inadvertently harmful to normal cells. n-Butyldiacatodoxorubicin (NBD) is a doxorubicin derivative that is converted in vivo to 2-pyrrolinodoxorubicin that is ∼ 1000-fold more active than doxorubicin. Because of its high potency, an efficient drug delivery system is needed in order to deliver NBD to the tumor site. To retain potent antitumor activity while reducing systemic toxicity, NBD was coupled to a thermally responsive macromolecular carrier. The macromolecular carrier is based on elastin-like polypeptide (ELP) which remains in solution at physiological temperature and accumulates in the tumor site when external hyperthermia is applied. The N-terminus of ELP was modified with the cell penetrating peptide (CPP) SynB1. SynB1 is a 19 amino acid peptide derived from porcine leukocytes which facilitates cellular uptake of the ELP carrier. NBD was attached to a terminal cysteine residue of ELP by conjugation of a 6-maleimidocaproyl hydrazone derivative of NBD. This NBD drug 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 NBD inhibited MCF-7 cells growth in the nanomolar range. In addition, inhibition of cell proliferation was enhanced two-fold when hyperthermia was applied and cell proliferation was accompanied by apoptosis, which was enhanced 3-fold in MCF-7 cells when SynB1-ELP-NBD aggregation was induced with hyperthermia. These results suggest that the SynB1-ELP-NBD conjugate is a promising candidate for investigating its thermally targeting properties against solid tumors in animal models.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3226. doi:10.1158/1538-7445.AM2011-3226" @default.
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- W2003860897 date "2011-04-15" @default.
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- W2003860897 title "Abstract 3226: In vitro evaluation of a thermally targeted conjugate of a highly potent doxorubicin derivative" @default.
- W2003860897 doi "https://doi.org/10.1158/1538-7445.am2011-3226" @default.
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