A Squalene-Based Nanomedicine for Oral Treatment of Colon Cancer.

Abstract

Nanotechnology offers many possibilities to improve drug treatments, including with regard to drug pharmacology. The current study reports a simple approach to improve cisplatin efficacy in the treatment of colon cancer through the creation of orally administered squalenoylated nanoparticles loaded with cisplatin (SQ-CDDP NP). Cytotoxic effects of SQ-CDDP NP were assessed in human colonic cells and in mouse models of intestinal cancer. In cell culture, SQ-CDDP NP exhibited at least 10-fold greater cytotoxic potency compared with uncomplexed cisplatin, reflecting an enhancement in intracellular accumulation and DNA platination. Mechanistic investigations showed that SQ-CDDP NP stimulated ROS production, expression of heavy metal-inducible and stress-inducible genes, stress kinase cascades, and apoptosis. In ApcMin/+ mice, a model of intestinal tumorigenesis, oral administration of SQ-CDDP NP curtailed spontaneous tumor formation and azoxymethane-induced colon carcinogenesis with no apparent evidence of tissue toxicity. Our results offer preclinical validation of a nanocarrier formulation that can safely improve chemotherapeutic efficacy, address risks of drug resistance, and improve patient compliance by enabling oral administration. Cancer Res; 77(11); 2964-75. ©2017 AACR.

• Authors: Larissa Kotelevets, Eric Chastre, Joachim Caron, Julie Mougin, Gerard Bastian, Alain Pineau, Francine Walker, Therese Lehy, Didier Desmaële, Patrick Couvreur
• Journal: Cancer research (Cancer Res) Vol. 77 Issue 11 Pg. 2964-2975 (06 01 2017) ISSN: 1538-7445 [Electronic] United States
• PMID: 28416486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Antineoplastic Agents
• Squalene

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis
• Cell Proliferation
• Colonic Neoplasms (drug therapy, pathology)
• Disease Models, Animal
• Humans
• Mice
• Nanomedicine (methods)
• Squalene (therapeutic use)