Insights into the deep-tissue photothermal therapy in near-infrared II region based on tumor-targeted MoO2 nanoaggregates  

基于肿瘤靶向MoO2纳米聚集体的近红外区深组织光热治疗

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)

机构地区：[1]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 [2]Guangdong Provincial Engineering Technology Research Center for Optical Agriculture,College of Materials and Energy,South China Agricultural University,Guangzhou 510642,China [3]Department of Physics and Optoelectronic Engineering,Foshan University,Foshan 528000,China [4]Casey Eye Institute,Oregon Health and Science University,Portland,97239 Oregon,USA

出　　处：《Science China Materials》2020年第6期1085-1098,共14页中国科学（材料科学（英文版）

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).

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.

关 键 词：second near-infrared window photothermal therapy molybdenum oxide depth profile analysis Raman biochemical assay 

分 类 号：R730.5[医药卫生—肿瘤]