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.
| Original language | English |
|---|---|
| Pages (from-to) | 9035-9046 |
| Number of pages | 12 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 59 |
| Issue number | 19 |
| DOIs | |
| State | Published - 13 Oct 2016 |
Bibliographical note
Publisher Copyright:© 2016 American Chemical Society.
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
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