Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 131, Issue 41, Pages 14652-+Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja9071282
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Funding
- NCI [CA034992, 5U54CA11934]
- Centers of Cancer Nanotechnology Excellence (CCNEs)
- Koch Institute for Integrative Cancer Research
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Amine-functionalized polyvalent oligonucleotide gold nanoparticles (DNA-Au NPs) were derivatized with a cisplatin prodrug, and the resulting DNA-Au NP conjugates were used to internalize multiple platinum centers. A platinum(IV) complex, c,c,t-[Pt(NH3)(2)Cl-2(OH)(O2CCH2CH2CO2H)], was tethered to the surface of DNA-Au NPs through amide linkages. The platinum-tethered gold nanoparticles were taken into several cancer cells. The drop in intracellular pH facilitated reductive release of cisplatin from the prodrug, which then formed 1,2-d(GpG) intrastrand cross-links in the cell nuclei, as confirmed by an antibody specific for this adduct. The cytotoxicity of the platinum(IV) complex increases significantly in several cancer cell tines when the complex is attached to the surface of the DNA-Au NPs and in some instances exceeds that of cisplatin.
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