Immuno nanoparticles integrated electrical control of targeted cancer cell development using whole cell bioelectronic device.
Immuno nanoparticles integrated electrical control of targeted cancer cell development using whole cell bioelectronic device.
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作者：
Hondroulis E;Zhang R;Zhang C;Chen C;Ino K;Matsue T;Li CZ
细胞的电学特性决定了细胞的大部分功能，特别是发生在细胞膜上的功能。对这些电学性质的操纵可能会为癌症的治疗提供一个强大的电疗法选择，因为癌细胞已经被证明比正常的增殖细胞更具电负性。此前，我们使用电阻抗传感系统(EIS)研究了癌细胞SKOV3细胞和正常HUVEC细胞对低强度(2V/cm)交流电场的反应，确定了在不损害非肿瘤HUVEC的情况下，SKOV3细胞增殖抑制的最佳频率为200 kHz。在这项研究中，为了确定这些效应是否与细胞类型有关，我们将人乳腺腺癌细胞(MCF7)置于与之前测试的SKOV3相似的频率范围(50 kHz-2 MHz)。对于MCF7，使用EIS确定了100 kHz的最佳频率，这表明对所施加的场具有更高的灵敏度。进一步使用HER2抗体功能化金纳米颗粒(HER2-AuNPs)针对这两种类型的癌细胞进行了实验，以确定是否可以通过应用纳米颗粒来诱导增强电场强度，从而在不影响非癌性HUVEC和MCF10A的情况下杀死癌细胞，从而为开发一种无副作用的非侵入性癌症治疗方法提供了平台。EIS被用来监测对细胞活力的实时影响，并且在HER2-AuNPs和电场的作用下，MCF7的生长曲线明显下降，表明对培养中的细胞分裂具有特异性的抑制作用。为了进一步了解外加磁场对细胞的影响，采用Annexin V/ethD-III检测来确定细胞死亡机制，表明细胞凋亡。此外，还获得了掺入HER2-AuNPs前后SKOV3和MCF7的Zeta电位，表明纳米颗粒的掺入降低了Zeta电位。这项研究的结果将提高我们对癌细胞行为的基本理解，并为临床和药物输送应用确定最佳的电疗参数。
Electrical properties of cells determine most of the cellular functions, particularly ones which occur in the cell's membrane. Manipulation of these electrical properties may provide a powerful electrotherapy option for the treatment of cancer as cancerous cells have been shown to be more electronegative than normal proliferating cells. Previously, we used an electrical impedance sensing system (EIS) to explore the responses of cancerous SKOV3 cells and normal HUVEC cells to low intensity (<2 V/cm) AC electric fields, determining that the optimal frequency for SKOV3 proliferation arrest was 200 kHz, without harming the non-cancerous HUVECs. In this study, to determine if these effects are cell type dependant, human breast adenocarcinoma cells (MCF7) were subjected to a range of frequencies (50 kHz-2 MHz) similar to the previously tested SKOV3. For the MCF7, an optimal frequency of 100 kHz was determined using the EIS, indicating a higher sensitivity towards the applied field. Further experiments specifically targeting the two types of cancer cells using HER2 antibody functionalized gold nanoparticles (HER2-AuNPs) were performed to determine if enhanced electric field strength can be induced via the application of nanoparticles, consequently leading to the killing of the cancerous cells without affecting non cancerous HUVECs and MCF10a providing a platform for the development of a non-invasive cancer treatment without any harmful side effects. The EIS was used to monitor the real-time consequences on cellular viability and a noticeable decrease in the growth profile of the MCF7 was observed with the application of the HER2-AuNPs and the electric fields indicating specific inhibitory effects on dividing cells in culture. To further understand the effects of the externally applied field to the cells, an Annexin V/EthD-III assay was performed to determine the cell death mechanism indicating apoptosis. The zeta potential of the SKOV3 and the MCF7 before and after incorporation of the HER2-AuNPs was also obtained indicating a decrease in zeta potential with the incorporation of the nanoparticles. The outcome of this research will improve our fundamental understanding of the behavior of cancer cells and define optimal parameters of electrotherapy for clinical and drug delivery applications.
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DOI：
10.1073/pnas.2232479100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Hirsch, LR;Stafford, RJ;West, JL
通讯作者：
West, JL
影响因子：
5.6
作者：
CONE, CD;TONGIER, M
通讯作者：
TONGIER, M
影响因子：
50.5
作者：
Ménard, S;Casalini, P;Tagliabue, E
通讯作者：
Tagliabue, E
影响因子：
2
作者：
Hondroulis, Evangelia;Zhang, Zhiqi;Li, Chen-Zhong
通讯作者：
Li, Chen-Zhong
影响因子：
29.4
作者：
Kim, Jaeyun;Lee, Ji Eun;Hyeon, Taeghwan
通讯作者：
Hyeon, Taeghwan