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Near-infrared phototherapy for patient-derived orthotopic xenograft model of hepatocellular carcinoma in combination with indocyanine green.
Journal of Photochemistry and Photobiology B: Biology ( IF 5.4 ) Pub Date : 2020-06-14 , DOI: 10.1016/j.jphotobiol.2020.111938
Felix Hong 1 , Jae Sun Park 2 , Seung Won Kim 3 , Sang-Jae Park 4 , Seok-Ki Kim 1
Affiliation  

Background

Hepatocellular carcinoma notably takes up and retains indocyanine green (ICG). Here, we investigated whether patient-derived orthotopic xenograft of hepatocellular carcinoma could accumulate ICG and show full remission via phototherapy.

Methods

NIR light and ICG were tested for cytotoxicity in cancerous cell lines (Huh-7, Hep3B). Patient-derived orthotopic xenograft (PDoX) mice were subjected to phototherapy comprising of daily NIR exposure (0.5–1.75 W/cm2) and intravenous injection of ICG (5–20 mg/kg2). Moreover, NIR laser was flashed on individual mouse until hepatocellular carcinoma completely loss the fluorescence, as determined by NIR camera.

Results

Cytotoxicity increased in response to the input energy, but insufficient energy (< 150 joule/cm2) was irresponsive at all irradiances. NIR irradiance in the range of 0.5–1.75 W/cm2 took 5–7 days to elicit complete remission from PDoX mice in combination with 20 mg/kg ICG. In contrast, phototherapy could completely ablate hepatocellular carcinoma at 5–15 mg/kg ICG.

Conclusions

ICG could potentiate the tumoricidal ability of NIR light in a dose-dependent manner, and vice versa. Regardless of ICG dosage, however, phototherapy treated group showed a relatively high survival rate compared to the non-treated group. Notably, real-time phototherapy could halve the effective ICG dosage for full remission of deep-seated tumor.



中文翻译:

近红外光疗结合吲哚花青绿治疗肝癌患者原位异种移植模型。

背景

肝细胞癌明显吸收并保留吲哚菁绿(ICG)。在这里,我们调查了患者源性肝细胞癌原位异种移植物是否可以积聚ICG并通过光疗显示完全缓解。

方法

测试了NIR光和ICG在癌细胞系(Huh-7,Hep3B)中的细胞毒性。患者来源的原位异种移植(PDoX)小鼠接受光疗,包括每日近红外暴露(0.5-1.75 W / cm 2)和静脉注射ICG(5-20​​ mg / kg 2)。此外,NIR激光照在每只小鼠身上,直到肝细胞癌完全失去荧光为止,这是由NIR相机确定的。

结果

细胞毒性随着输入能量的增加而增加,但是在所有辐照下能量不足(<150焦耳/ cm 2)均无反应。在0.5–1.75 W / cm 2范围内的NIR辐照需要5–7天才能与20 mg / kg ICG结合,使PDoX小鼠完全缓解。相比之下,光疗可以以5-15 mg / kg ICG完全消融肝细胞癌。

结论

ICG可以剂量依赖的方式增强NIR光的杀肿瘤能力,反之亦然。但是,无论ICG剂量如何,与未治疗组相比,光疗治疗组均显示出较高的存活率。值得注意的是,实时光疗可以使深部肿瘤完全缓解的有效ICG剂量减半。

更新日期:2020-06-23
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