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将单壁碳纳米管与低电压电刺激相结合,以提高纳米药物在肿瘤中的蓄积,从而实现有效的癌症治疗。

Combining the single-walled carbon nanotubes with low voltage electrical stimulation to improve accumulation of nanomedicines in tumor for effective cancer therapy.

作者信息

Lee Pei-Chi, Peng Cheng-Liang, Shieh Ming-Jium

机构信息

Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan.

Isotope Application Division, Institute of Nuclear Energy Research, P.O. Box 3-27, Longtan, Taoyuan 325, Taiwan.

出版信息

J Control Release. 2016 Mar 10;225:140-51. doi: 10.1016/j.jconrel.2016.01.038. Epub 2016 Jan 23.

Abstract

Effective delivery of biomolecules or functional nanoparticles into target sites has always been the primary objective for cancer therapy. We demonstrated that by combining single-walled carbon nanotubes (SWNTs) with low-voltage (LV) electrical stimulation, biomolecule delivery can be effectively enhanced through reversible electroporation (EP). Clear pore formation in the cell membrane is observed due to LV (50V) pulse electrical stimulation amplified by SWNTs. The cell morphology remains intact and high cell viability is retained. This modality of SWNT + LV pulses can effectively transfer both small molecules and macromolecules into cells through reversible EP. The results of animal studies also suggest that treatment with LV pulses alone cannot increase vascular permeability in tumors unless after the injection of SWNTs. The nanoparticles can cross the permeable vasculature, which enhances their accumulation in the tumor tissue. Therefore, in cancer treatment, both SWNT + LV pulse treatment followed by the injection of LIPO-DOX® and SWNT/DOX + LV pulse treatment can increase tumor inhibition and delay tumor growth. This novel treatment modality applied in a human cancer xenograft model can provide a safe and effective therapy using various nanomedicines in cancer treatment.

摘要

将生物分子或功能性纳米颗粒有效递送至靶位点一直是癌症治疗的首要目标。我们证明,通过将单壁碳纳米管(SWNTs)与低电压(LV)电刺激相结合,可通过可逆电穿孔(EP)有效增强生物分子递送。由于SWNTs放大了LV(50V)脉冲电刺激,在细胞膜中观察到明显的孔形成。细胞形态保持完整,细胞活力高。SWNT + LV脉冲这种方式可通过可逆EP将小分子和大分子有效转移到细胞中。动物研究结果还表明,单独用LV脉冲治疗不能增加肿瘤中的血管通透性,除非在注射SWNTs之后。纳米颗粒可以穿过渗透性血管,这增强了它们在肿瘤组织中的积累。因此,在癌症治疗中,先进行SWNT + LV脉冲治疗然后注射LIPO-DOX®以及SWNT/DOX + LV脉冲治疗均可增强肿瘤抑制并延缓肿瘤生长。这种应用于人类癌症异种移植模型的新型治疗方式可为癌症治疗中使用各种纳米药物提供安全有效的疗法。

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