Drug conjugation to hyaluronan widens therapeutic indications for ovarian cancer

Isabella Monia Montagner, Anna Merlo, Debora Carpanese, Gaia Zuccolotto, Davide Renier, Monica Campisi, Gianfranco Pasut, Paola Zanovello, Antonio Rosato

Research output: Contribution to journalArticlepeer-review

Abstract

Management of ovarian cancer still requires improvements in therapeutic options. A drug delivery strategy was tested that allows specific targeting of tumor cells in combination with a controlled release of a cytotoxic molecule. To this aim, the efficacy of a loco-regional intraperitoneal treatment with a bioconjugate (ONCOFID-S) derived by chemical linking of SN-38, the active metabolite of irinotecan (CPT-11), to hyaluronan was assessed in a mouse model of ovarian carcinomatosis. In vitro, the bioconjugate selectively interacted with ovarian cancer cells through the CD44 receptor, disclosed a dose-dependent tumor growth inhibition efficacy comparable to that of free SN-38 drug, and inhibited Topoisomerase I function leading to apoptosis by a mechanism involving caspase-3 and -7 activation and PARP cleavage. In vivo, the intraperitoneal administration of ONCOFID-S in tumor-bearing mice did not induce inflammation, and evidenced an improved therapeutic efficacy compared with CPT-11. In conclusion, SN-38 conjugation to hyaluronan significantly improved the profile of in vivo tolerability and widened the field of application of irinotecan. Therefore, this approach can be envisaged as a promising therapeutic strategy for loco-regional treatment of ovarian cancer.

Original languageEnglish
Pages (from-to)373-381
Number of pages9
JournalOncoscience
Volume2
Issue number4
DOIs
Publication statusPublished - 2015

Keywords

  • Bioconjugate
  • Hyaluronan
  • Ovarian cancer
  • SN-38
  • Tumor targeting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Drug conjugation to hyaluronan widens therapeutic indications for ovarian cancer'. Together they form a unique fingerprint.

Cite this