Monitoring of the tumor response to nano-graphene oxide-mediated photothermal/photodynamic therapy by diffusion-weighted and BOLD MRI

Monitoring of the tumor response to nano-graphene oxide-mediated photothermal/photodynamic therapy by diffusion-weighted and BOLD MRI
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通过扩散加权和 BOLD MRI 监测肿瘤对纳米氧化石墨烯介导的光热/光动力治疗的反应

DOI:
10.1039/c6nr02012g
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发表时间:
2016-01-01
期刊:
影响因子:
6.7
通讯作者:
Zhang, Fan
Zhang, Fan
中科院分区:
材料科学2区
文献类型:
--
作者:
Cao, Jianbo;An, Hengqing;Zhang, Fan

文献摘要

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光热疗法(PTT)和光动力疗法(PDT)是有前途的癌症治疗方式。由于每种方式都有其自身的优点和局限性,因此人们对开发可以共同递送两种方案以增强肿瘤治疗的方法感兴趣。在这些努力中,纳米氧化石墨烯介导的光疗最近引起了广泛关注。纳米氧化石墨烯具有宽的吸收光谱,并且可以高效地负载光敏剂,例如二氢卟酚e6。负载二氢卟酚e6和PEG化的纳米石墨烯(GO-PEG-Ce 6)可以在660 nm、808 nm或两者下激发,以诱导PDT、PTT或PDT/PTT组合。尽管治疗的潜力,有一个缺乏的诊断工具,可以监测他们的治疗反应,在一个非侵入性和预后的方式,这种能力是迫切需要的技术的转化和翻译。在本研究中,我们在GO-PEG-Ce 6介导的PTT、PDT或PTT/PDT后进行了弥散加权和血氧水平依赖性(BOLD)磁共振成像(MRI)。我们发现,有效的PTT后,有一个显着增加的扩散加权成像(DWI)图中的肿瘤表观扩散系数(ADC)值;同时,一个有效的PDT导致增加的R-2* 在BOLD图像。在这两种情况下,ADC/R-2* 增加的幅度与治疗结果相关。更有趣的是,当应用PTT/PDT组合时观察到协同治疗功效,并且该组合与比单独使用任一模式时更大的ADC和R-2* 增加相关。特别地,诱导ADC值的最显著的短期增加(>70%)的PTT/PDT条件在长期中引起最有效的肿瘤控制,其中60%的经治疗的动物在60天后无肿瘤。这些结果表明,DWI和BOLD MRI的组合作为一种工具,用于准确的监测和预后的光疗,这是非常有价值的方法的未来发展的巨大希望。
Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities. Because each modality has its own set of advantages and limitations, there has been interest in developing methods that can co-deliver the two regimens for enhanced tumor treatment. Among the efforts, nano-graphene oxide-mediated phototherapies have recently attracted much attention. Nano-graphene oxide has a broad absorbance spectrum and can be loaded with photosensitizers, such as chlorin e6, with high efficiency. Chlorin e6-loaded and PEGylated nano-graphene (GO-PEG-Ce6) can be excited at 660 nm, 808 nm, or both, to induce PDT, PTT, or PDT/PTT combination. Despite the potential of the treatments, there is a lack of a diagnostic tool which can monitor their therapeutic response in a noninvasive and prognostic manner; such an ability is urgently needed for the transformation and translation of the technologies. In this study, we performed diffusion-weighted and blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) after GO-PEG-Ce6-mediated PTT, PDT, or PTT/PDT. We found that after efficient PTT, there is a significant increase of the tumor apparent diffusion coefficient (ADC) value in diffusion-weighted imaging (DWI) maps; meanwhile, an efficient PDT led to an increase of R-2* in BOLD images. In both the cases, the amplitude of the ADC/R-2* increase was correlated with the treatment outcomes. More interestingly, a synergistic treatment efficacy was observed when the PTT/PDT combination was applied, and the combination was associated with a greater ADC and R-2* increase than when either modality was used alone. In particular, the PTT/PDT condition that induced the most dramatic short-term increase of the ADC value (>70%) caused the most effective tumor control in the long-run, with 60% of the treated animals being tumor-free after 60 days. These results suggest the great promise of the combination of DWI and BOLD MRI as a tool for accurate monitoring and prognosis of phototherapies, which is of great value to the future developments of the methodologies.