Nano-photosensitizers Engineered to Generate a Tunable Mix of Reactive Oxygen Species, for Optimizing Photodynamic Therapy, Using a Microfluidic Device.
Nano-photosensitizers Engineered to Generate a Tunable Mix of Reactive Oxygen Species, for Optimizing Photodynamic Therapy, Using a Microfluidic Device.
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DOI：
10.1021/cm403505s
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发表时间：
2014-02-25
影响因子：
8.6
通讯作者：
Kopelman, Raoul
中科院分区：
文献类型：
--
作者：
Yoon, Hyung Ki;Lou, Xia;Chen, Yu-Chih;Lee, Yong-Eun Koo;Yoon, Euisik;Kopelman, Raoul
关键词：
这项工作的目的是设计光敏剂嵌入纳米颗粒(NPs)，以产生光动力疗法(PDT)所需的最佳活性氧物种(ROS)。一种改进的合成方法，加上改进的分析工具，导致了更有效的光动力疗法。为提高肿瘤光动力疗法的疗效，合成了以聚乙二醇二甲基丙烯酸酯(PEGDMA，Mn550)为交联剂的亚甲基蓝(MB)偶联聚丙烯酰胺纳米粒(PAA NPs)。与以前使用的较短的交联剂相比，长交联剂PEGDMA增加了共轭MB分子之间的距离，从而避免了激发态或物种的自猝灭，并增强了NP基质的透氧性。用传统的无烟-9，10-二丙酸(ADPA)氧化速率动力学方法评价了MB-PEGDMA PAA纳米颗粒的总ROS产量。我们还应用了单线态氧传感器绿(SOSG)，以选择性地推导出单线态氧(1O2)的产生速率。这一分析使我们能够研究基于不同MB负荷的ROS组成混合。为了有效地获得ROS产量和细胞杀伤效率之间的相关性，使用微流控芯片器件来提供来自LED的均匀光照明，以用于快速PDT效率测试，从而能够在仅使用少量NPS样品的情况下同时进行多项测量。这提供了多路综合的PDT效率分析，通过测量各种MB-PEGDMA PAA纳米粒使用C6胶质瘤癌细胞的光剂量依赖的细胞杀伤效果，确定了高PDT效率的PAA基质中接近最佳的MB负载量。
This work is aimed at engineering photosensitizer embedded nanoparticles (NPs) that produce optimal amount of reactive oxygen species (ROS) for photodynamic therapy (PDT). A revised synthetic approach, coupled with improved analytical tools, resulted in more efficient PDT. Specifically, methylene blue (MB) conjugated polyacrylamide nanoparticles (PAA NPs), with a polyethylene glycol dimethacrylate (PEGDMA, Mn 550) cross-linker, were synthesized so as to improve the efficacy of cancer PDT. The long cross-linker chain, PEGDMA, increases the distance between the conjugated MB molecules so as to avoid self-quenching of the excited states or species, and also enhances the oxygen permeability of the NP matrix, when compared to the previously used shorter cross-linker. The overall ROS production from the MB–PEGDMA PAA NPs was evaluated using the traditional way of monitoring the oxidation rate kinetics of anthracence-9,10-dipropionic acid (ADPA). We also applied singlet oxygen sensor green (SOSG) so as to selectively derive the singlet oxygen (1O2) production rate. This analysis enabled us to investigate the ROS composition mix based on varied MB loading. To effectively obtain the correlation between the ROS productivity and the cell killing efficacy, a microfluidic chip device was employed to provide homogeneous light illumination from an LED for rapid PDT efficacy tests, enabling simultaneous multiple measurements while using only small amounts of NPs sample. This provided multiplexed, comprehensive PDT efficacy assays, leading to the determination of a near optimal loading of MB in a PAA matrix for high PDT efficacy by measuring the light-dose-dependent cell killing effects of the various MB–PEGDMA PAA NPs using C6 glioma cancer cells.
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