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碳纳米管介导的内体/溶酶体光热破坏逆转MCF-7/ADR细胞对阿霉素的耐药性

Carbon Nanotube-Mediated Photothermal Disruption of Endosomes/Lysosomes Reverses Doxorubicin Resistance in MCF-7/ADR Cells.

作者信息

Pai Chin-Ling, Chen Yu-Chun, Hsu Chia-Yen, Su Hong-Lin, Lai Ping-Shan

出版信息

J Biomed Nanotechnol. 2016 Apr;12(4):619-29. doi: 10.1166/jbn.2016.2133.

Abstract

Cancer is the leading cause of human death worldwide. Although many scientists work to fight this disease, multiple drug resistance is a predominant obstacle for effective cancer therapy. In drug-resistant MCF-7/ADR cells, the acidic organelles with lower pH value than normal one can cause the protonation of anthracycline drugs, inducing drug accumulation in these organelles. In this study, single-walled carbon nanotubes with polyethylene glycol phospholipids surface modification (PEGylated SWNTs) were utilized as near infrared-activated drug carriers for doxorubicin (DOX) delivery against MCF-7/ADR cells. Our results showed that a concentration-dependent temperature increase was observed in a solution of PEGylated SWNTs with 808 nm laser irradiation, whereas a water solution showed no significant changes in temperature under a thermal camera using the same irradiation dose. Interestingly, PEGylated DOX-SWNTs enhanced the nuclear accumulation of DOX with 808 nm irradiation whereas free DOX or PEGylated DOX-SWNTs revealed discrete red spots in MCF-7/ADR cells by confocal microscopic observation. Cell viability of PEGylated DOX-SWNTs-treated cells was also significantly decreased after 808 nm laser irradiation. Thus, photothermally activated PEGylated SWNTs can be a potential nanocarrier to deliver DOX into cancer cells and successfully overcome drug-resistant behavior in MCF-7/ADR breast cancer cells.

摘要

癌症是全球人类死亡的主要原因。尽管许多科学家致力于对抗这种疾病,但多重耐药性是有效癌症治疗的主要障碍。在耐药的MCF-7/ADR细胞中,pH值低于正常水平的酸性细胞器可导致蒽环类药物质子化,促使药物在这些细胞器中蓄积。在本研究中,聚乙二醇磷脂表面修饰的单壁碳纳米管(PEG化单壁碳纳米管)被用作近红外激活的药物载体,用于向MCF-7/ADR细胞递送阿霉素(DOX)。我们的结果表明,用808 nm激光照射时,PEG化单壁碳纳米管溶液中观察到浓度依赖性的温度升高,而在相同照射剂量下,使用热成像仪观察发现水溶液温度无明显变化。有趣的是,经808 nm照射后,PEG化阿霉素-单壁碳纳米管增强了阿霉素的核内蓄积,而通过共聚焦显微镜观察发现,游离阿霉素或PEG化阿霉素-单壁碳纳米管在MCF-7/ADR细胞中呈现离散的红色斑点。经808 nm激光照射后,PEG化阿霉素-单壁碳纳米管处理的细胞活力也显著降低。因此,光热激活的PEG化单壁碳纳米管可能是一种潜在的纳米载体,可将阿霉素递送至癌细胞,并成功克服MCF-7/ADR乳腺癌细胞的耐药行为。

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