Encapsulation of c-myc antisense oligodeoxynucleotides in lipid particles improves antitumoral efficacy in vivo in a human melanoma line

Carlo Leonetti, Annamaria Biroccio, Barbara Benassi, Annarita Stringaro, Antonella Stoppacciaro, Sean C. Semple, Gabriella Zupi

Research output: Contribution to journalArticlepeer-review

Abstract

Phosphorothioate c-myc antisense oligodeoxynucleotides [S]ODNs (free INX-6295) were encapsulated in a new liposome formulation and the antitumor activity was compared to the unencapsulated antisense in a human melanoma xenograft. The systemic administration of INX-6295 encapsulated in stabilized antisense lipid particles (SALP INX-6295) improved plasma AUC (area under the plasma concentration-time curve) and initial half-life of free INX-6295, resulting in a significant enhancement in tumor accumulation and improvement in tumor distribution of antisense oligodeoxynucleotides. Animals treated with SALP INX-6295 exhibited a prolonged reduction of c-myc expression, reduced tumor growth and increased mice survival. When administered in combination with cisplatin (DDP), SALP INX-6295 produced a complete tumor regression in approximately 30% of treated mice, which persisted for at least 60 days following the first cycle of treatment. Finally, the median survival of mice treated with DDP/SALP INX-6295 increased by 105% compared to 84% for animals treated with the combination DDP/free INX-6295. These data indicate that the biological activity and the therapeutic efficacy of c-myc antisense therapy may be improved when these agents are administered in lipid-based delivery systems.

Original languageEnglish
Pages (from-to)459-468
Number of pages10
JournalCancer Gene Therapy
Volume8
Issue number6
DOIs
Publication statusPublished - 2001

Keywords

  • Antisense oligodeoxynucleotides
  • Liposome
  • Melanoma
  • Preclinical therapy
  • Xenotransplantation

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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