Measurement of Cyanine Dye Photobleaching in Photosensitizer Cyanine Dye Conjugates Could Help in Optimizing Light Dosimetry for Improved Photodynamic Therapy of Cancer.

Measurement of Cyanine Dye Photobleaching in Photosensitizer Cyanine Dye Conjugates Could Help in Optimizing Light Dosimetry for Improved Photodynamic Therapy of Cancer.
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光敏剂氰染料偶联物中氰氨酸染料光漂白的测量可以帮助优化光剂量测定法,以改善癌症的光动力疗法。

DOI:
10.3390/molecules23081842
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发表时间:
2018-07-24
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Pandey RK
Pandey RK
中科院分区:
其他
文献类型:
--
作者:
James NS;Cheruku RR;Missert JR;Sunar U;Pandey RK

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光动力学疗法(PDT)治疗癌症依赖于三种主要成分:光敏剂(PS)、光和氧。由于这些成分是相互依赖的,并在PDT的动态过程中变化,评估PDT疗效可能不是微不足道的。因此,有必要在PDT期间开发治疗前规划、在线监测和剂量测定策略,这对于两个或更多个发色团系统变得更加关键,例如,我们实验室开发的用于癌症的荧光成像和PDT的PS-CD(光敏剂-花菁染料)缀合物。在这项研究中,我们观察到可变光剂量的显著影响;(i)高光通量和通量率(光剂量:135 J/cm 2,注量率:75 mW/cm 2)和(ii)低光通量和通量率(128 J/cm 2和14 mW/cm 2以及128 J/cm 2和7 mW/cm 2)在PS-CD缀合物的单个发色团的光漂白及其长期肿瘤响应中的作用。通过荧光成像间歇地评估PS-NIR荧光团缀合物的近红外(NIR)区域处的荧光。在PDT过程中,由来自PS的单线态氧引起的荧光损失、光漂白被连续映射。PDT后通过每天测量肿瘤大小来评估肿瘤反应(携带Colon 26肿瘤的BALB/c小鼠)。我们的研究结果表明,PS和CD之间的独特的光漂白动力学速率。有趣的是,与较高的光通量相比,暴露在低光通量下的肿瘤显示出减少的光漂白和增强的长期PDT疗效。PS-CD缀合物中NIR荧光团的存在提供了荧光成像和监测CD部分对于大且深的肿瘤的光漂白速率以及实时评估PDT肿瘤响应的机会。
Photodynamic therapy (PDT) of cancer is dependent on three primary components: photosensitizer (PS), light and oxygen. Because these components are interdependent and vary during the dynamic process of PDT, assessing PDT efficacy may not be trivial. Therefore, it has become necessary to develop pre-treatment planning, on-line monitoring and dosimetry strategies during PDT, which become more critical for two or more chromophore systems, for example, PS-CD (Photosensitizer-Cyanine dye) conjugates developed in our laboratory for fluorescence-imaging and PDT of cancer. In this study, we observed a significant impact of variable light dosimetry; (i) high light fluence and fluence rate (light dose: 135 J/cm2, fluence rate: 75 mW/cm2) and (ii) low light fluence and fluence rate (128 J/cm2 and 14 mW/cm2 and 128 J/cm2 and 7 mW/cm2) in photobleaching of the individual chromophores of PS-CD conjugates and their long-term tumor response. The fluorescence at the near-infrared (NIR) region of the PS-NIR fluorophore conjugate was assessed intermittently via fluorescence imaging. The loss of fluorescence, photobleaching, caused by singlet oxygen from the PS was mapped continuously during PDT. The tumor responses (BALB/c mice bearing Colon26 tumors) were assessed after PDT by measuring tumor sizes daily. Our results showed distinctive photobleaching kinetics rates between the PS and CD. Interestingly, compared to higher light fluence, the tumors exposed at low light fluence showed reduced photobleaching and enhanced long-term PDT efficacy. The presence of NIR fluorophore in PS-CD conjugates provides an opportunity of fluorescence imaging and monitoring the photobleaching rate of the CD moiety for large and deeply seated tumors and assessing PDT tumor response in real-time.
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