| First Author | Kotelevets L | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 11 | Pages | 2964-2975 |
| PubMed ID | 28416486 | Mgi Jnum | J:242485 |
| Mgi Id | MGI:5905487 | Doi | 10.1158/0008-5472.CAN-16-1741 |
| Citation | Kotelevets L, et al. (2017) A Squalene-Based Nanomedicine for Oral Treatment of Colon Cancer. Cancer Res 77(11):2964-2975 |
| abstractText | 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. (c)2017 AACR. |
