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Molecules 2009, 14(6), 1999-2015; doi:10.3390/molecules14061999
Article

Application of Thermally Responsive Elastin-like Polypeptide Fused to a Lactoferrin-derived Peptide for Treatment of Pancreatic Cancer

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Received: 11 May 2009; in revised form: 31 May 2009 / Accepted: 3 June 2009 / Published: 4 June 2009
(This article belongs to the Special Issue Macromolecules Applied to Pharmaceutics)
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Abstract: A well characterized, peptide derivative of bovine lactoferrin, L12, has been shown to possess anticancer properties in multiple cell lines. However, adverse side effects in normal tissues and poor plasma kinetics that hinder the clinical effectiveness of current chemotherapeutics also deter the potential for effective delivery of this L12 peptide. To overcome these limitations, we have developed an Elastin-like polypeptide (ELP) carrier that has the potential to thermally target therapeutic peptides and chemotherapeutics to a tumor site. The coding sequence of ELP was modified with the L12 peptide at the C-terminus and a membrane transduction domain derived from the HIV-1 Tat protein at the N-terminus (Tat-ELP-L12). The thermally responsive Tat-ELP1-L12 is soluble in aqueous solutions at 37°C but aggregates near 41°C, which makes Tat-ELP1-L12 ideal for targeting to solid tumors on application of focused hyperthermia. We observed that under hyperthermia conditions at 42°C, Tat-ELP1-L12 mediated cytotoxicity in MIA PaCa-2 pancreatic adenocarcinoma cells was enhanced by nearly thirty-fold. We investigated the mechanisms of cell death and found evidence of mitochondrial membrane depolarization and caspase activation, which are characteristic of apoptosis, as well as, increased membrane permeability, as shown by LDH release. These results suggest that Tat-ELP1-L12 possesses cytotoxic properties to cancer cells in vitro and may have the potential to provide an effective vehicle to thermally target solid tumors.
Keywords: Elastin-like polypeptide; L12; hyperthermia; thermal targeting; drug delivery; pancreatic cancer Elastin-like polypeptide; L12; hyperthermia; thermal targeting; drug delivery; pancreatic cancer
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Massodi, I.; Thomas, E.; Raucher, D. Application of Thermally Responsive Elastin-like Polypeptide Fused to a Lactoferrin-derived Peptide for Treatment of Pancreatic Cancer. Molecules 2009, 14, 1999-2015.

AMA Style

Massodi I, Thomas E, Raucher D. Application of Thermally Responsive Elastin-like Polypeptide Fused to a Lactoferrin-derived Peptide for Treatment of Pancreatic Cancer. Molecules. 2009; 14(6):1999-2015.

Chicago/Turabian Style

Massodi, Iqbal; Thomas, Emily; Raucher, Drazen. 2009. "Application of Thermally Responsive Elastin-like Polypeptide Fused to a Lactoferrin-derived Peptide for Treatment of Pancreatic Cancer." Molecules 14, no. 6: 1999-2015.



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