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

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

Research output: Contribution to journalArticlepeer-review

391 Scopus citations

Abstract

(Chemical Equation Presented) 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)2Cl2(OH) (O2CCH2CH 2CO2H)], 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.

Original languageEnglish (US)
Pages (from-to)14652-14653
Number of pages2
JournalJournal of the American Chemical Society
Volume131
Issue number41
DOIs
StatePublished - Oct 21 2009

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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