Biophysical and morphological effects of nanodiamond/nanoplatinum solution (DPV576) on metastatic murine breast cancer cells in vitro
Biophysical and morphological effects of nanodiamond/nanoplatinum solution (DPV576) on metastatic murine breast cancer cells in vitro
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DOI：
10.1088/0957-4484/25/46/465101
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发表时间：
2014-11-21
期刊：
影响因子：
3.5
通讯作者：
Gimzewski, James K.
中科院分区：
文献类型：
--
作者：
Ghoneum, Alia;Zhu, Huanqi;Gimzewski, James K.
纳米颗粒由于其微小的尺寸和独特的化学性质，最近作为用于治疗癌症的药物递送系统获得了越来越多的关注。然而，很少有研究在细胞和亚细胞尺度上测试与转移性癌细胞上的纳米颗粒相关的生物物理变化。在这里，我们研究了癌细胞的机械和形态学特性，通过测量细胞杨氏模量的变化，使用AFM，丝状伪足收缩（FR）的时间推移光学显微镜成像和丝状伪足解体的高分辨率AFM成像的细胞治疗后的纳米粒子。在本研究中，监测了暴露于分散在水溶液中的纳米金刚石/纳米铂混合物（DPV 576）后活鼠转移性乳腺癌细胞（4 T1）的纳米机械变化。结果显示，在用DPV 576处理后2小时，杨氏模量以剂量依赖性方式降低。观察到20 min时部分FR和40 min时完全FR。此外，随时间（分钟）测量的回缩距离（以微米计）的分析表明，15%v/v的DPV 576浓度产生最高的FR率。此外，DPV 576处理的细胞显示出丝状伪足解体和崩解的早期迹象。这项研究证明了细胞硬度的变化，并跟踪了DPV 576治疗后转移性乳腺癌细胞的早期结构变化，这可能对基于纳米金刚石/纳米铂的癌细胞治疗和化疗药物致敏作用具有重要意义。
Nanoparticles have recently gained increased attention as drug delivery systems for the treatment of cancer due to their minute size and unique chemical properties. However, very few studies have tested the biophysical changes associated with nanoparticles on metastatic cancer cells at the cellular and sub-cellular scales. Here, we investigated the mechanical and morphological properties of cancer cells by measuring the changes in cell Young's Modulus using AFM, filopodial retraction (FR) by time lapse optical light microscopy imaging and filopodial disorganization by high resolution AFM imaging of cells upon treatment with nanoparticles. In the current study, nanomechanical changes in live murine metastatic breast cancer cells (4T1) post exposure to a nanodiamond/nanoplatinum mixture dispersed in aqueous solution (DPV576), were monitored. Results showed a decrease in Young's modulus at two hours post treatment with DPV576 in a dose dependent manner. Partial FR at 20 min and complete FR at 40 min were observed. Moreover, analysis of the retraction distance (in microns) measured over time (minutes), showed that a DPV576 concentration of 15% v/v yielded the highest FR rate. In addition, DPV576 treated cells showed early signs of filopodial disorganization and disintegration. This study demonstrates the changes in cell stiffness and tracks early structural alterations of metastatic breast cancer cells post treatment with DPV576, which may have important implications in the role of nanodiamond/nanoplatinum based cancer cell therapy and sensitization to chemotherapy drugs.