Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads

被引：467

作者：

Dhar, Shanta ^{[2
]}

Daniel, Weston L. ^{[1
,3
]}

Giljohann, David A. ^{[1
,3
]}

Mirkin, Chad A. ^{[1
,3
]}

Lippard, Stephen J. ^{[2
]}

机构：

[1] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA

[2] MIT, Dept Chem, Cambridge, MA 02139 USA

[3] Northwestern Univ, Int Inst Nanotechnol, Evanston, IL 60208 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2009年 / 131卷 / 41期

关键词：

CISPLATIN; COMPLEXES;

D O I：

10.1021/ja9071282

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

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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页码：14652 / +

页数：4

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