Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads
Author(s)Dhar, Shanta; Daniel, Weston L.; Giljohann, David A.; Mirkin, Chad A.; Lippard, Stephen J.
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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(NH[subscript 3])[subscript 2]Cl[subscript 2](OH)(O[subscript 2]CCH[subscript 2]CH[subscript 2]CO[subscript 2]H)], 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 lines when the complex is attached to the surface of the DNA-Au NPs and in some instances exceeds that of cisplatin.
DepartmentMassachusetts Institute of Technology. Department of Chemistry
Journal of the American Chemical Society
American Chemical Society (ACS)
Dhar, Shanta, Weston L. Daniel, David A. Giljohann, Chad A. Mirkin, and Stephen J. Lippard. “Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads.” Journal of the American Chemical Society 131, no. 41 (October 21, 2009): 14652-14653.
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