Organic Stealth Nanoparticles for Highly Effective in Vivo Near-Infrared Photothermal Therapy of Cancer
Organic Stealth Nanoparticles for Highly Effective in Vivo Near-Infrared Photothermal Therapy of Cancer
复制标题
有机隐形纳米粒子可高效体内近红外光热治疗癌症
DOI：
10.1021/nn301539m
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发表时间：
2012-06-01
期刊：
影响因子：
17.1
通讯作者：
Liu, Zhuang
中科院分区：
文献类型：
--
作者：
Cheng, Liang;Yang, Kai;Liu, Zhuang
近年来，已经开发了广泛的近红外（NIR）光吸收纳米材料，主要是无机材料，用于癌症的光热治疗（PTT）。在这项工作中，我们开发了一种新的有机PTT剂的基础上聚-（3，4-乙撑二氧噻吩）：聚（4-苯乙烯磺酸盐）（PEDOT：PSS），导电聚合物混合物具有强近红外吸收，在体内光热治疗癌症。在用带电聚合物逐层包覆然后与支化聚乙二醇（PEG）缀合之后，所获得的PEDOT：PSS-PEG纳米颗粒在生理环境中高度稳定，并且在静脉注射后表现出具有长的血液循环半衰期的隐形行为。结果，观察到PEDOT：PSS-PEG的极高的体内肿瘤摄取，这归因于肿瘤增强的渗透性和保留效应。我们进一步使用PEDOT：PSS-PEG作为PTT试剂用于体内癌症治疗，并在低激光功率密度的NIR光照射下在小鼠肿瘤模型中实现了优异的治疗效果。全面的血液测试和仔细的组织学检查显示，在我们的治疗剂量下，PEDOT：PSS-PEG在40天内对小鼠没有明显的毒性。据我们所知，这项工作是第一次使用全身给药的导电聚合物纳米颗粒在动物体内进行高效的PTT治疗，并鼓励进一步探索这些有机纳米材料用于癌症治疗诊断应用。
In recent years, a wide range of near-infrared (NIR) light absorbing nanomaterials, mostly inorganic ones, have been developed for photothermal therapy (PTT) of cancer. In this work, we develop a novel organic PTT agent based on poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS), a conductive polymer mixture with strong NIR absorbance, for in vivo photothermal treatment of cancer. After being layer-by-layer coated with charged polymers and then conjugated with branched polyethylene glycol (PEG), the obtained PEDOT:PSS-PEG nanoparticles are highly stable in the physiological environment and exhibit a stealth-like behavior after intravenous injection with a long blood circulation half-life. As a result an extremely high in vivo tumor uptake of PEDOT:PSS-PEG attributed to the tumor-enhanced permeability and retention effect is observed. We further use PEDOT:PSS-PEG as a PTT agent for in vivo cancer treatment and realize excellent therapeutic efficacy in a mouse tumor model under NIR light irradiation at a low laser power density. Comprehensive blood tests and careful histological examination reveal no apparent toxicity of PEDOT:PSS-PEG to mice at our treated dose within 40 days. To our best knowledge, this work is the first to use systemically administrated conductive polymer nanoparticles for highly effective in vivo PTT treatment in animals and encourages further explorations of those organic nanomaterials for cancer theranostic applications.