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与基质金属蛋白酶-1抗体偶联的铁金双金属纳米颗粒在口腔癌诊疗中的应用

Oral Cancer Theranostic Application of FeAu Bimetallic Nanoparticles Conjugated with MMP-1 Antibody.

作者信息

Tsai Meng-Tsan, Sun Ying-Sui, Keerthi Murugan, Panda Asit Kumar, Dhawan Udesh, Chang Yung-Hsiang, Lai Chih-Fang, Hsiao Michael, Wang Huey-Yuan, Chung Ren-Jei

机构信息

Department of Electrical Engineering, Chang Gung University, 259, Wenhua 1st Rd., Taoyuan City 33302, Taiwan.

Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou Branch, 5, Fuxing St., Guishan Dist., Taoyuan City 33305, Taiwan.

出版信息

Nanomaterials (Basel). 2021 Dec 27;12(1):61. doi: 10.3390/nano12010061.

Abstract

Metastatic oral squamous cell carcinoma (SCC) displays a poor disease prognosis with a 5-year survival rate of 39%. Chemotherapy has emerged as the mainstream treatment against small clusters of cancer cells but poses more risks than benefits for metastatic cells due to the non-specificity and cytotoxicity. To overcome these obstacles, we conjugated antibodies specific for matrix metalloproteinase-1 (MMP-1), a prognostic biomarker of SCC, to iron-gold bimetallic nanoparticles (FeAu NPs) and explored the capability of this complex to target and limit SSC cell growth via magnetic field-induced hyperthermia. Our results showed that 4.32 ± 0.79 nm sized FeAu NPs were superparamagnetic in nature with a saturation magnetization (Ms) of 5.8 emu/g and elevated the media temperature to 45 °C, confirming the prospect to deliver hyperthermia. Furthermore, conjugation with MMP-1 antibodies resulted in a 3.07-fold higher uptake in HSC-3 (human tongue squamous cell carcinoma) cells as compared to L929 (fibroblast) cells, which translated to a 5-fold decrease in cell viability, confirming SCC targeting. Finally, upon magnetic stimulation, MMP-1-FeAu NPs conjugate triggered 89% HSC-3 cellular death, confirming the efficacy of antibody-conjugated nanoparticles in limiting SCC growth. The synergistic effect of biomarker-specific antibodies and magnetic nanoparticle-induced hyperthermia may open new doors towards SCC targeting for improved disease prognosis.

摘要

转移性口腔鳞状细胞癌(SCC)的疾病预后较差,5年生存率为39%。化疗已成为针对小簇癌细胞的主流治疗方法,但由于其非特异性和细胞毒性,对转移细胞而言风险大于益处。为克服这些障碍,我们将基质金属蛋白酶-1(MMP-1,SCC的一种预后生物标志物)特异性抗体与铁金双金属纳米颗粒(FeAu NPs)偶联,并探索了这种复合物通过磁场诱导热疗靶向和抑制SSC细胞生长的能力。我们的结果表明,尺寸为4.32±0.79 nm的FeAu NPs本质上是超顺磁性的,饱和磁化强度(Ms)为5.8 emu/g,能将培养基温度升高至45°C,证实了其进行热疗的前景。此外,与MMP-1抗体偶联后,HSC-3(人舌鳞状细胞癌)细胞的摄取量比L929(成纤维细胞)细胞高3.07倍,这导致细胞活力降低5倍,证实了对SCC的靶向作用。最后,在磁刺激下,MMP-1-FeAu NPs偶联物引发了89%的HSC-3细胞死亡,证实了抗体偶联纳米颗粒在抑制SCC生长方面的功效。生物标志物特异性抗体与磁性纳米颗粒诱导热疗的协同效应可能为改善疾病预后的SCC靶向治疗打开新的大门。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7404/8746455/72249fb2f97e/nanomaterials-12-00061-g001.jpg

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