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

doi:10.1021/ja9071282

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

Chemistry

Research output: Contribution to journal › Article › peer-review

488 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 language	English (US)
Pages (from-to)	14652-14653
Number of pages	2
Journal	Journal of the American Chemical Society
Volume	131
Issue number	41
DOIs	https://doi.org/10.1021/ja9071282
State	Published - Oct 21 2009

ASJC Scopus subject areas

General Chemistry
Biochemistry
Catalysis
Colloid and Surface Chemistry

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title = "Polyvalent oligonucleotide gold nanoparticle conjugates as delivery vehicles for platinum(IV) warheads",

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.",

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AU - Dhar, Shanta

AU - Daniel, Weston L.

AU - Giljohann, David A.

AU - Mirkin, Chad A.

AU - Lippard, Stephen J.

PY - 2009/10/21

Y1 - 2009/10/21

N2 - (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.

AB - (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.

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

Abstract

ASJC Scopus subject areas

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