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The inclusion complex of 4-hydroxynonenal with a polymeric derivative of ß-cyclodextrin enhances the antitumoral efficacy of the aldehyde in several tumor cell lines and in a three-dimensional human melanoma model.
Pizzimenti, Stefania; Ciamporcero, Eric; Pettazzoni, Piergiorgio; Osella-Abate, Simona; Novelli, Mauro; Toaldo, Cristina; Husse, Miriam; Daga, Martina; Minelli, Rosalba; Bisazza, Agnese; Ferruti, Paolo; Ranucci, Elisabetta; Grazia Bernengo, Maria; Dianzani, Chiara; Biasi, Fiorella; Cavalli, Roberta; Barrera, Giuseppina.
Afiliación
  • Pizzimenti S; Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy. Electronic address: stefania.pizzimenti@unito.it.
  • Ciamporcero E; Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy.
  • Pettazzoni P; Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy.
  • Osella-Abate S; Section of Dermatology, Department of Medical Sciences, University of Turin, 10125 Turin, Italy.
  • Novelli M; Section of Dermatology, Department of Medical Sciences, University of Turin, 10125 Turin, Italy.
  • Toaldo C; Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy.
  • Husse M; Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy.
  • Daga M; Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy.
  • Minelli R; Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy.
  • Bisazza A; Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy.
  • Ferruti P; Department of Chemistry, University of Milan, Milano, Italy.
  • Ranucci E; Department of Chemistry, University of Milan, Milano, Italy.
  • Grazia Bernengo M; Section of Dermatology, Department of Medical Sciences, University of Turin, 10125 Turin, Italy.
  • Dianzani C; Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy.
  • Biasi F; Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy.
  • Cavalli R; Section of Dermatology, Department of Medical Sciences, University of Turin, 10125 Turin, Italy.
  • Barrera G; Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy.
Free Radic Biol Med ; 65: 765-777, 2013 Dec.
Article en En | MEDLINE | ID: mdl-23811007
4-Hydroxynonenal (HNE) is the most studied end product of the lipoperoxidation process, by virtue of its relevant biological activity. The antiproliferative and proapoptotic effects of HNE have been widely demonstrated in a great variety of tumor cell types in vitro. Thus, it might represent a promising new molecule in anticancer therapy strategies. However, the extreme reactivity of this aldehyde, as well as its insolubility in water, a limiting factor for drug bioavailability, and its rapid degradation by specific enzymes represent major obstacles to its possible in vivo application. Various strategies can used to overcome these problems. One of the most attractive strategies is the use of nanovehicles, because loading drugs into nanosized structures enhances their stability and solubility, thus improving their bioavailability and their antitumoral effectiveness. Several natural or synthetic polymers have been used to synthesize nanosized structures and, among them, ß-cyclodextrin (ßCD) polymers are playing a very important role in drug formulation by virtue of the ability of ßCD to form inclusion compounds with a wide range of solid and liquid molecules by molecular complexation. Moreover, several ßCD derivatives have been designed to improve their physicochemical properties and inclusion capacities. Here we report that the inclusion complex of HNE with a derivative of ßCD, the ßCD-poly(4-acryloylmorpholine) conjugate (PACM-ßCD), enhances the aldehyde stability. Moreover, the inclusion of HNE in PACM-ßCD potentiates its antitumor effects in several tumor cell lines and in a more complex system, such as a human reconstructed skin carrying melanoma tumor cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Beta-Ciclodextrinas / Aldehídos / Melanoma / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2013 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Beta-Ciclodextrinas / Aldehídos / Melanoma / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2013 Tipo del documento: Article Pais de publicación: Estados Unidos