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

Polyvalent oligonucleotide gold nanoparticle conjugates as delivery vehicles for platinum(IV) warheads.
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DOI:
10.1021/ja9071282
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发表时间:
2009-10-21
影响因子:
15
通讯作者:
Lippard, Stephen J.
Lippard, Stephen J.
中科院分区:
化学1区
文献类型:
--
作者:
Dhar, Shanta;Daniel, Weston L.;Giljohann, David A.;Mirkin, Chad A.;Lippard, Stephen J.

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胺官能化的多价寡核苷酸金纳米粒子(DNA-Au NP)与顺铂前药衍生化,所得DNA-Au NP缀合物用于内化多个铂中心。将铂(IV)络合物c,c,t-[Pt(NH3)2Cl 2(OH)(O2 CCH 2CH 2CO 2 H)]通过酰胺键连接到DNA-Au NPs的表面。将铂系链金纳米颗粒(Pt-DNA-Au NPs)带入几种癌细胞中。细胞内pH值的下降促进了顺铂从前药中的还原性释放,然后在细胞核中形成1,2-d(GpG)链内交联,这一点通过对该加合物具有特异性的抗体证实。当铂(IV)络合物附着于DNA-Au NP的表面时,铂(IV)络合物的细胞毒性在几种癌细胞系中显著增加,并且在某些情况下超过顺铂的细胞毒性。
Amine-functionalized polyvalent oligonucleotide gold nanoparticles (DNA-Au NP) 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)2Cl2(OH)(O2CCH2CH2CO2H)], was tethered to the surface of DNA-Au NPs through amide linkages. The platinum-tethered gold nanoparticles (Pt-DNA-Au NPs) 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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