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抗体偶联纳米颗粒免疫热疗选择性靶向并清除单个癌细胞。

Immuno-hyperthermia effected by antibody-conjugated nanoparticles selectively targets and eradicates individual cancer cells.

机构信息

Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.

Graduate School of Science and Engineering, Ehime University, Matsuyama, Japan.

出版信息

Cell Cycle. 2021 Jul;20(13):1221-1230. doi: 10.1080/15384101.2021.1915604. Epub 2021 Jun 19.

Abstract

Hyperthermia has been used for cancer therapy for a long period of time, but has shown limited clinical efficacy. Induction-heating hyperthermia using the combination of magnetic nanoparticles (MNPs) and an alternating magnetic field (AMF), termed magnetic hyperthermia (MHT), has previously shown efficacy in an orthotopic mouse model of disseminated gastric cancer. In the present study, superparamagnetic iron oxide nanoparticles (SPIONs), a type of MNP, were conjugated with an anti-HER2 antibody, trastuzumab and termed anti-HER2-antibody-linked SPION nanoparticles (anti-HER2 SPIONs). Anti-HER2 SPIONs selectively targeted HER2-expressing cancer cells co-cultured along with normal fibroblasts and HER2-negative cancer cells and caused apoptosis only in the HER2-expressing individual cancer cells. The results of the present study show proof-of-concept of a novel hyperthermia technology, immuno-MHT for selective cancer therapy, that targets individual cancer cells. AMF: alternating magnetic field; DDW: double distilled water; DMEM: Dulbecco's Modified Eagle's; Medium; f: frequency; FBS: fetal bovine serum; FITC: Fluorescein isothiocyanate; GFP: green fluorescent protein; H: amplitude; Hsp: heat shock protein; MHT: magnetic hyperthermia; MNPs: magnetic nanoparticles; PI: propidium iodide; RFP: red fluorescent protein; SPION: superparamagnetic iron oxide (FeO) nanoparticle.

摘要

热疗在癌症治疗中已有很长的应用历史,但疗效有限。将磁性纳米颗粒(MNPs)与交变磁场(AMF)结合使用的感应加热热疗,即磁热疗(MHT),在胃癌原位模型中已显示出疗效。在本研究中,超顺磁性氧化铁纳米颗粒(SPIONs),一种 MNP,与抗 HER2 抗体曲妥珠单抗偶联,并被命名为抗 HER2 抗体连接的 SPION 纳米颗粒(抗 HER2 SPIONs)。抗 HER2 SPIONs 选择性地靶向与正常成纤维细胞和 HER2 阴性癌细胞共培养的 HER2 表达癌细胞,并仅在 HER2 表达的单个癌细胞中引起细胞凋亡。本研究结果证明了一种新型热疗技术,即免疫磁热疗(immuno-MHT),用于针对单个癌细胞的选择性癌症治疗的概念验证。AMF:交变磁场;DDW:双蒸水;DMEM:杜尔贝科改良伊格尔培养基;f:频率;FBS:胎牛血清;FITC:异硫氰酸荧光素;GFP:绿色荧光蛋白;H:振幅;Hsp:热休克蛋白;MHT:磁热疗;MNPs:磁性纳米颗粒;PI:碘化丙啶;RFP:红色荧光蛋白;SPION:超顺磁性氧化铁(FeO)纳米颗粒。

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