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Title: 5-Fluorouracil-loaded poly(ε-caprolactone) nanoparticles combined with phage E gene therapy as a new strategy against colon cancer
Authors: Ortiz, Raúl
Prados, José
Melguizo, Consolación
Arias, José L
Ruiz, M Adolfina
Alvarez, Pablo J
Caba, Octavio
Luque, Raquel
Segura, Ana
Aránega, Antonia
metadata.dc.contributor.authoraffiliation: [Ortiz,R; Prados,J; Melguizo,C; Alvarez,PJ; Caba,O; Aránega,A] Institute of Biopathology and Regenerative Medicine (IBIMER). [Arias,JL; Ruiz, MA] Department of Pharmacy and Pharmaceutical Technology, University of Granada, Granada, Spain. [Caba,O] Department of Health Science, University of Jaén, Jaén, Spain. [Luque,R] Service of Medical Oncology, Virgen de las Nieves Hospital, Granada, Spain. [Segura,A] CSIC-Estacion Experimental del Zaidin, Department of Environmental Protection, Granada, Spain.
Keywords: colon cancer;combined therapy;5-fluorouracil;gene therapy;E gene;poly (ε-caprolactone);Neoplasias del Colon;Terapia de Gen;Humanos;Fluorouracilo;Nanopartículas;Antineoplásicos;Apoptosis
metadata.dc.subject.mesh: Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colonic Neoplasms
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Gene Therapy
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::Uracil::Fluorouracil
Medical Subject Headings::Technology, Industry, Agriculture::Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Issue Date: 6-Jan-2012
Publisher: Dove Medical Press
Citation: Ortiz R, Prados J, Melguizo C, Arias JL, Ruiz MA, Álvarez PJ, et al. 5-Fluorouracil-loaded poly(ε-caprolactone) nanoparticles combined with phage E gene therapy as a new strategy against colon cancer. Int J Nanomedicine. 2012;7:95-107
Abstract: This work aimed to develop a new therapeutic approach to increase the efficacy of 5-fluorouracil (5-FU) in the treatment of advanced or recurrent colon cancer. 5-FU-loaded biodegradable poly(ε-caprolactone) nanoparticles (PCL NPs) were combined with the cytotoxic suicide gene E (combined therapy). The SW480 human cancer cell line was used to assay the combined therapeutic strategy. This cell line was established from a primary adenocarcinoma of the colon and is characterized by an intrinsically high resistance to apoptosis that correlates with its resistance to 5-FU. 5-FU was absorbed into the matrix of the PCL NPs during synthesis using the interfacial polymer disposition method. The antitumor activity of gene E from the phage ϕX174 was tested by generating a stable clone (SW480/12/E). In addition, the localization of E protein and its activity in mitochondria were analyzed. We found that the incorporation of 5-FU into PCL NPs (which show no cytotoxicity alone), significantly improved the drug's anticancer activity, reducing the proliferation rate of colon cancer cells by up to 40-fold when compared with the nonincorporated drug alone. Furthermore, E gene expression sensitized colon cancer cells to the cytotoxic action of the 5-FU-based nanomedicine. Our findings demonstrate that despite the inherent resistance of SW480 to apoptosis, E gene activity is mediated by an apoptotic phenomenon that includes modulation of caspase-9 and caspase-3 expression and intense mitochondrial damage. Finally, a strongly synergistic antiproliferative effect was observed in colon cancer cells when E gene expression was combined with the activity of the 5-FU-loaded PCL NPs, thereby indicating the potential therapeutic value of the combined therapy.
Description: Original research
metadata.dc.identifier.doi: 10.2147/IJN.S26401
ISSN: 1176-9114 (Print)
1178-2013 (Online)
Appears in Collections:01- Artículos - Hospital Virgen de las Nieves

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