Targeted single-wall carbon nanotube-mediated Pt(IV) prodrug delivery using folate as a homing device.
Targeted single-wall carbon nanotube-mediated Pt(IV) prodrug delivery using folate as a homing device.
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靶向的单壁碳纳米管介导的PT（IV）前药使用叶酸作为归巢装置。
DOI：
10.1021/ja803036e
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发表时间：
2008-08-27
影响因子：
15
通讯作者：
Lippard, Stephen J.
中科院分区：
文献类型：
--
作者：
Dhar, Shanta;Liu, Zhuang;Thomale, Juergen;Dai, Hongjie;Lippard, Stephen J.
大多数低分子量铂抗癌药物具有短的血液循环时间，这反映在它们降低的肿瘤摄取和细胞内DNA结合。制备并表征了在轴向位置含有叶酸衍生物（FA）的式c，c，t-[Pt（NH 3）2 Cl 2（O 2 CCH 2 CH 2 CO 2 H）（O 2 CCH 2 CH 2 CONH-PEG-FA）]（1）的铂（IV）络合物。叶酸提供了一种靶向高度过表达叶酸受体（FR）的人类细胞的方法。化合物1通过多个酰胺键连接到胺官能化的单壁碳纳米管（SWNT-PL-PEG-NH 2）的表面，以使用SWNT作为铂弹头的“长船递送系统”，将其携带到肿瘤细胞并在Pt（IV）细胞内还原为Pt（II）时释放顺铂。SWNT tethered 1选择性破坏FR（+）与FR（-）细胞的能力证明了其靶向在其表面上过表达FR的肿瘤细胞的能力。通过荧光显微镜对荧光标记的单壁碳纳米管进行定位，证明了单壁碳纳米管通过内吞作用将携带叶酸的Pt（IV）货物运送到FR（+）癌细胞中。一旦进入细胞内，从长船桨还原释放后形成的顺铂进入细胞核并与其靶核DNA反应，如通过细胞提取物的铂原子吸收光谱法所测定。形成的主要顺铂1，2-intrastrand d（GpG）的核DNA上的交联证明通过使用该加合物的单克隆抗体特异性。SWNT系链化合物1是第一个将靶向和递送结合到同一分子中的构建体;它也是第一个证明Pt（IV）前药的细胞内还原导致核DNA中的顺式-{Pt（（NH3）2} 1，2-链内d（GpG）交联的构建体。
Most low molecular weight platinum anticancer drugs have short blood circulation times that are reflected in their reduced tumor uptake and intracellular DNA binding. A platinum(IV) complex of the formula c,c,t-[Pt(NH3)2Cl2(O2CCH2CH2CO2H)(O2CCH2CH2CONH-PEG-FA)] (1) containing a folate derivative (FA) at an axial position was prepared and characterized. Folic acid offers a means of targeting human cells that highly overexpress the folate receptor (FR). Compound 1 was attached to the surface of an amine functionalized single walled carbon nanotube (SWNT-PL-PEG-NH2) through multiple amide linkages to use the SWNTs as a “longboat delivery system” for the platinum warhead, carrying it to the tumor cell and releasing cisplatin upon intracellular reduction of Pt(IV) to Pt(II). The ability of SWNT tethered 1 to destroy selectively FR(+) vs FR(−) cells demonstrated its ability to target tumor cells that overexpress the FR on their surface. That the SWNTs deliver the folate-bearing Pt(IV) cargos into FR(+) cancer cells by endocytosis was demonstrated by the localization of fluorophorelabeled SWNTs using fluorescence microscopy. Once inside the cell, cisplatin formed upon reductive release from the longboat oars enters the nucleus and reacts with its target nuclear DNA, as determined by platinum atomic absorption spectroscopy of cell extracts. Formation of the major cisplatin 1,2-intrastrand d(GpG) cross-links on the nuclear DNA was demonstrated by use of a monoclonal antibody specific for this adduct. The SWNT-tethered compound 1 is the first construct in which both targeting and delivery have been incorporated into the same molecule; it is also the first demonstration that intracellular reduction of a Pt(IV) pro-drug leads to the cis-{Pt((NH3)2} 1,2-intrastrand d(GpG) crosslink in nuclear DNA.
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影响因子：
15
作者：
Georgakilas, V;Kordatos, K;Hirsch, A
通讯作者：
Hirsch, A
影响因子：
3
作者：
Hall, MD;Dillon, CT;Hambley, TW
通讯作者：
Hambley, TW
DOI：
10.1073/pnas.97.2.745
发表时间：
2000-01-18
影响因子：
11.1
作者：
Arunachalam, B;Phan, UT;Cresswell, P
通讯作者：
Cresswell, P
碳纳米管将 GFP 基因传递到哺乳动物细胞中
影响因子：
3.2
作者：
Gao, LZ;Nie, L;Yan, XY
通讯作者：
Yan, XY
影响因子：
15
作者：
Kam, NWS;Dai, HJ
通讯作者：
Dai, HJ