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Cancer Res. 2017 Jun 1;77(11):2964-2975. doi: 10.1158/0008-5472.CAN-16-1741. Epub 2017 Apr 17.

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

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Institut Galien Paris-Sud, UMR 8612, CNRS; Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
INSERM U938, Centre de Recherche Saint-Antoine, Paris, France.
Institut Universitaire de Cancérologie, Pierre et Marie Curie (UPMC) Sorbonne Universités, Paris, France.
INSERM U1149, CNRS ERL8252, Centre de Recherche sur l'Inflammation, Paris, France.
Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, Faculté de Médecine, Site Bichat, Paris, France.
Département de Pharmacologie, Pierre et Marie Curie (UPMC) Sorbonne Universités, Faculté de Médecine, Site Pitié-Salpêtrière, Paris, France.
Laboratoire de Toxicologie, Faculté de Pharmacie, Nantes, France.
Assistance publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine Bichat-Claude Bernard, Service d'Anatomo-Pathologie, Paris, France.
Institut Galien Paris-Sud, UMR 8612, CNRS; Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.


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.

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