In vivo anticancer activity of rhomboidal Pt(II) metallacycles
In vivo anticancer activity of rhomboidal Pt(II) metallacycles
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DOI：
10.1073/pnas.1418712111
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发表时间：
2014-12-30
影响因子：
11.1
通讯作者：
Olenyuk, Bogdan Z.
中科院分区：
文献类型：
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作者：
Grishagin, Ivan V.;Pollock, J. Bryant;Olenyuk, Bogdan Z.
新型抗肿瘤药物的开发，具有高效率的抑制肿瘤生长，具有低毒性的非肿瘤组织，并表现出快速定位在靶向肿瘤部位是一个正在进行的研究在化学，癌症生物学和药理学的接口的途径。超分子金属配位络合物（SCC）具有明确的形状和几何形状，并且在它们的内化后，SCC可以影响细胞和组织中的多种致癌信号通路。我们研究了两种菱形Pt（II）基SCC的摄取、细胞内定位和抗肿瘤活性。使用A549和HeLa细胞中的激光扫描共聚焦显微镜来确定细胞内组装体的摄取和定位，并在小鼠皮下研究它们对肿瘤生长的影响。肿瘤异种移植模型。SCC在研究浓度的整个范围内（1 nM-5 μ M）可溶于细胞培养基中，是无毒的，并且显示出降低皮下肿瘤生长速率的功效。小鼠肿瘤异种移植物。这些特性揭示了Pt（II）基SCC作为治疗剂用于未来生物医学应用的潜力。
The development of novel antitumor agents that have high efficacy in suppressing tumor growth, have low toxicity to nontumor tissues, and exhibit rapid localization in the targeted tumor sites is an ongoing avenue of research at the interface of chemistry, cancer biology, and pharmacology. Supramolecular metal-based coordination complexes (SCCs) have well-defined shapes and geometries, and upon their internalization, SCCs could affect multiple oncogenic signaling pathways in cells and tissues. We investigated the uptake, intracellular localization, and antitumor activity of two rhomboidal Pt(II)-based SCCs. Laser-scanning confocal microscopy in A549 and HeLa cells was used to determine the uptake and localization of the assemblies within cells and their effect on tumor growth was investigated in mouse s.c. tumor xenograft models. The SCCs are soluble in cell culture media within the entire range of studied concentrations (1 nM-5 mu M), are nontoxic, and showed efficacy in reducing the rate of tumor growth in s.c. mouse tumor xenografts. These properties reveal the potential of Pt(II)-based SCCs for future biomedical applications as therapeutic agents.