biostudies-literatureUnknown14(12)Khoury AFour platinum(IV) prodrugs incorporating a biotin moiety to selectively target cancer cells were synthesised, characterised, and their biological activity assessed. All complexes exhibited exceptional in vitro cytotoxicity against a panel of cancer cell lines, with [Pt(5,6-dimethyl-1,10-phenanthroline)(1<i>S</i>,2<i>S</i>-diaminocyclohexane)(biotin)(hydroxido)](NO₃)₂, (<b>2</b>) exhibiting the lowest GI₅₀ of 4 nM in the prostate Du145 cancer cell line. Each complex displayed significantly enhanced activity compared to cisplatin, with <b>2</b> being 1000-fold more active in the HT29 colon cancer cell line. Against the MCF-7 breast cancer cell line, in which high levels of biotin receptors are expressed, <b>2</b>, [Pt(4,7-dimethoxy-1,10-phenanthroline)(1<i>S</i>,2<i>S</i>-diaminocyclohexane)(biotin)(hydroxido)](NO₃)₂, (<b>3</b>), and [Pt(5-methyl-1,10-phenanthroline)(1<i>S</i>,2<i>S</i>-diaminocyclohexane)(biotin)(hydroxido)](NO₃)₂, (<b>4</b>) exhibited enhanced activity compared to their platinum(II) cores, with <b>4</b> being 6-fold more active than its platinum(II) precursor. Furthermore, <b>3</b> exhibited 3-fold greater selectivity towards MCF-7 breast cancer cells compared to MCF10A breast healthy cells, and this was further confirmed by platinum uptake studies, which showed <b>3</b> to have almost 3-fold greater uptake in MCF-7 cells, compared to MCF10A cells. The results show that lipophilicity and selectivity both contributed to the cellular uptake of <b>1</b>-<b>4</b>; however, this was not always translated to the observed cytotoxicity.Pharmaceutics2780https://www.ebi.ac.uk/biostudies/studies/S-EPMC9853328biostudies-literaturePotent Platinum(IV) Prodrugs That Incorporate a Biotin Moiety to Selectively Target Cancer Cells.PMC9853328Karan SGordon CPAldrich-Wright JRSakoff JAKhoury AGilbert JfalsePotent Platinum(IV) Prodrugs That Incorporate a Biotin Moiety to Selectively Target Cancer Cells.Four platinum(IV) prodrugs incorporating a biotin moiety to selectively target cancer cells were synthesised, characterised, and their biological activity assessed. All complexes exhibited exceptional in vitro cytotoxicity against a panel of cancer cell lines, with [Pt(5,6-dimethyl-1,10-phenanthroline)(1<i>S</i>,2<i>S</i>-diaminocyclohexane)(biotin)(hydroxido)](NO₃)₂, (<b>2</b>) exhibiting the lowest GI₅₀ of 4 nM in the prostate Du145 cancer cell line. Each complex displayed significantly enhanced activity compared to cisplatin, with <b>2</b> being 1000-fold more active in the HT29 colon cancer cell line. Against the MCF-7 breast cancer cell line, in which high levels of biotin receptors are expressed, <b>2</b>, [Pt(4,7-dimethoxy-1,10-phenanthroline)(1<i>S</i>,2<i>S</i>-diaminocyclohexane)(biotin)(hydroxido)](NO₃)₂, (<b>3</b>), and [Pt(5-methyl-1,10-phenanthroline)(1<i>S</i>,2<i>S</i>-diaminocyclohexane)(biotin)(hydroxido)](NO₃)₂, (<b>4</b>) exhibited enhanced activity compared to their platinum(II) cores, with <b>4</b> being 6-fold more active than its platinum(II) precursor. Furthermore, <b>3</b> exhibited 3-fold greater selectivity towards MCF-7 breast cancer cells compared to MCF10A breast healthy cells, and this was further confirmed by platinum uptake studies, which showed <b>3</b> to have almost 3-fold greater uptake in MCF-7 cells, compared to MCF10A cells. The results show that lipophilicity and selectivity both contributed to the cellular uptake of <b>1</b>-<b>4</b>; however, this was not always translated to the observed cytotoxicity.2022-01-01T00:00:00Z2022 Dec2025-04-26T00:39:31.284Z2025-04-06T09:46:54.514ZS-EPMC98533283655927310.3390/pharmaceutics14122780