摘要
Research on deep-tissue photothermal therapy(PTT)in the near-infrared II(NIR-II,1000–1350 nm)region has bloomed in recent years,owing to higher maximum permissible exposure and deeper tissue penetration over that in the near-infrared I(NIR-I,650–950 nm)region.However,more details need to be uncovered to facilitate a fundamental understanding of NIR-ⅡPTT.Herein,a tumor-targeted therapeutic nanosystem based on NIR-responsive molybdenum oxide(MoO2)nanoaggregates was fabricated.The photothermal conversion capabilities of MoO2 in the NIR-I andⅡregions were investigated step by step,from a simple tissue phantom to a three-dimensional cellular system,and further to a tumor-bearing animal model.NIR-Ⅱlaser exhibited a lower photothermal attenuation coefficient(0.541 at1064 nm)in a tissue phantom compared with its counterpart(0.959 at 808 nm),which allows it to be more capable of deeptissue PTT in vitro and in vivo.Depth profile analysis elucidated a negative correlation between the microstructural collapse of tumor tissue and the penetration depth.Moreover,the depth-related tumor ablation was also studied by Raman fingerprint analysis,which demonstrated the major biochemical compositional disturbances in photothermal ablated tumor tissues,providing fundamental knowledge to NIR-Ⅱdeeptissue photothermal therapy.
近红外II区(NIR-II,1000–1350 nm)的光热治疗(PTT)近年来发展迅速,其最大允许照射量和组织穿透深度均高于近红外I区(NIR-I,650–950 nm).金纳米结构、单壁碳纳米管、钯纳米颗粒等材料已作为高效的NIR-II光热消融肿瘤的治疗剂被探索,而关于NIR-II PTT后的深部组织转化的细节信息还有待发掘.本文系统地研究了NIR-II深层组织PTT术后肿瘤的深度分布.基于NIR响应的氧化钼(MoO2)纳米聚集体的肿瘤靶向治疗纳米系统,我们开展了光热肿瘤治疗.为了验证PTT后的组织深度相关细节,我们建立了三个不同层次的模型:组织模型、三维细胞系统模型与荷瘤动物模型.NIR-II激光在组织模型中表现出较低的光热衰减系数(1064 nm时为0.541),而在808 nm时该值为0.959,这使得它在体内外都能更好地进行深层组织PTT.深度剖面分析表明肿瘤组织的显微结构破坏与穿透深度呈负相关.同时,我们利用拉曼光谱对PTT后组织深度图谱的生化指纹变化进行解码,揭示了光热消融肿瘤组织中主要的生化成分紊乱,为NIR-II深层组织光热治疗提供了理论基础.
作者
Yanxian Guo
Yang Li
Wolun Zhang
Hongru Zu
Haihong Yu
Dongling Li
Honglian Xiong
Tristan THormel
Chaofan Hu
Zhouyi Guo
Zhiming Liu
郭艳先;李阳;张沃伦;祖鸿儒;余海红;李东铃;熊红莲;Tristan THormel;胡超凡;郭周义;刘智明(Guang Provincial Key Laboratory of Laser Life Science&SATCM Third Grade Laboratory of Chinese Medicine and Photonics Technology,College of Biophotonics,South China Normal University,Guangzhou,510631,China;Guangdong Provincial Engineering Technology Research Center for Optical Agriculture,College of Materials and Energy,South China Agricultural University,Guangzhou 510642,China;Department of Physics and Optoelectronic Engineering,Foshan University,Foshan 528000,China;Casey Eye Institute,Oregon Health and Science University,Portland,97239 Oregon,USA)
基金
This work was supported by the National Natural Science Foundation of China(11874021,61675072,81601534 and 51402207)
the Science and Technology Project of Guangdong Province of China(2017A020215059)
the Science and Technology Project of Guangzhou City(201904010323).
