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. 2009 Oct 21;131(41):14652-3.
doi: 10.1021/ja9071282.

Polyvalent oligonucleotide gold nanoparticle conjugates as delivery vehicles for platinum(IV) warheads

Shanta Dhar  1 , Weston L Daniel, David A Giljohann, Chad A Mirkin, Stephen J Lippard
Affiliations

Polyvalent oligonucleotide gold nanoparticle conjugates as delivery vehicles for platinum(IV) warheads

Shanta Dhar et al. J Am Chem Soc. .

Erratum in

  • J Am Chem Soc. 2010 Dec 8;132(48):17335
  • J Am Chem Soc. 2010 Mar 3;132(8):2845

Abstract

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(3))(2)Cl(2)(OH)(O(2)CCH(2)CH(2)CO(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.

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Figures

Figure 1
Figure 1
Live cell imaging of HeLa cells upon incubation with platinum-tethered Cy5-DNA-Au NPs for 6 h (A), 12 h (B), and colocalization of the particles with the cytoplasmic microtubules (C). Hoechst 33342 was used for nuclear staining. Scale bars: 20 μm.
Figure 2
Figure 2
Cytotoxicity profiles of Pt-DNA-Au NP (formula image), cisplatin (■), 1 (formula image) with U2OS, A549, HeLa, and PC3 cells.
Scheme 1
Scheme 1
Construction of Pt-DNA-Au NP
See this image and copyright information in PMC

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