A site-selective hyaluronan-interferonα2a conjugate for the treatment of ovarian cancer

Isabella Monia Montagner, Anna Merlo, Debora Carpanese, Anna Dalla Pietà, Anna Mero, Antonella Grigoletto, Arianna Loregian, Davide Renier, Monica Campisi, Paola Zanovello, Gianfranco Pasut, Antonio Rosato

Research output: Contribution to journalArticle

Abstract

While interferon alpha (IFNα) is used in several viral and cancer contexts, its efficacy against ovarian cancer (OC) is far from being incontrovertibly demonstrated and, more importantly, is hindered by heavy systemic side effects. To overcome these issues, here we propose a strategy that allows a targeted delivery of the cytokine, by conjugating IFNα2a with an aldehyde-modified form of hyaluronic acid (HA). The resulting HA-IFNα2a bioconjugate was biochemically and biologically characterized. The conjugation with HA did not substantially modified both the antiviral function and the anti-proliferative activity of the cytokine. Moreover, the induction of STAT1 phosphorylation and of a specific gene expression signature in different targets was retained. In vivo optical imaging biodistribution showed that the i.p.-injected HA-IFNα2a persisted into the peritoneal cavity longer than IFNα2a without being toxic for intraperitoneal organs, thus potentially enhancing the loco-regional therapeutic effect. Indeed, in OC xenograft mouse models bioconjugate significantly improved survival as compared to the free cytokine. Overall, HA-IFNα2a bioconjugate disclosed an improved anticancer efficacy, and can be envisaged as a promising loco-regional treatment for OC.

Original languageEnglish
Pages (from-to)79-89
Number of pages11
JournalJournal of Controlled Release
Volume236
DOIs
Publication statusPublished - Aug 28 2016

Keywords

  • HAylation
  • Hyaluronan
  • Interferon
  • Ovarian cancer
  • Tumor targeting

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Montagner, I. M., Merlo, A., Carpanese, D., Dalla Pietà, A., Mero, A., Grigoletto, A., Loregian, A., Renier, D., Campisi, M., Zanovello, P., Pasut, G., & Rosato, A. (2016). A site-selective hyaluronan-interferonα2a conjugate for the treatment of ovarian cancer. Journal of Controlled Release, 236, 79-89. https://doi.org/10.1016/j.jconrel.2016.06.033