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      1. Author :
        Abu Ammar, Aiman; Raveendran, Raji; Gibson, Dan; Nassar, Taher; Benita, Simon
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2016
      5. Publication :
        Journal of Medicinal Chemistry
      6. Products :
      7. Volume :
        59
      8. Issue :
        19
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS; IVIS BLI in vivo
      12. Abstract :
        Side effects and acquired resistance by cancer cells limit the use of platinum anticancer drugs. Modification of oxaliplatin (OXA) into a lipophilic Pt(IV) complex [Pt(DACH)(OAc)(OPal)(ox)] (1), containing both lipophilic and hydrophilic axial ligands, was applied to improve performance and facilitate incorporation into polymeric nanoparticles. Complex 1 exhibited unique potency against a panel of cancer cells, including cisplatin-resistant tumor cells. [Pt(DACH)(OAc)(OPal)(ox)] incorporated nanoparticles (2) presented a mean diameter of 146 nm with encapsulation yields above 95% as determined by HPLC. Complexes 1 and 2 showed enhanced in vitro cellular Pt accumulation, DNA platination, and antiproliferative effect compared to OXA. Results of an orthotopic intraperitoneal model of metastatic ovarian cancer (SKOV-3) and a xenograft subcutaneous model of colon (HCT-116) tumor in SCID-bg mice showed that the activity of 1 and 2 significantly decreased tumor growth rates compared to control and OXA treatment groups. Consequently, these findings warrant further development toward clinical translation.
      13. URL :
        http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00955
      14. Call Number :
        PKI @ user @ 13289
      15. Serial :
        20160