Development of visualization and analysis methods for evaluating intratumoral nanoparticle kinetics for tumor-targeted drug delivery using F?rster resonance energy transfer in vivo live imaging and tissue clearing techniques
Development of visualization and analysis methods for evaluating intratumoral nanoparticle kinetics for tumor-targeted drug delivery using F?rster resonance energy transfer in vivo live imaging and tissue clearing techniques
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开发可视化和分析方法，使用 F?rster 共振能量转移体内实时成像和组织透明技术来评估肿瘤靶向药物输送的肿瘤内纳米颗粒动力学
DOI：
10.1016/j.jpba.2022.115127
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发表时间：
2023
影响因子：
3.4
通讯作者：
Chono Sumio
中科院分区：
文献类型：
--
作者：
Togami Kohei;Ishizawa Kiyomi;Yasuda Mio;Tada Hitoshi;Chono Sumio
在这项研究中，在BxPC 3荷瘤小鼠中改进了用于评估纳米颗粒作为药物递送系统在肿瘤组织中的动力学的成像方法。首先，选择Förster共振能量转移（FRET）实时成像来定量评估小鼠肿瘤组织中的纳米颗粒动力学。简言之，将1，1 ′-双十八烷基-3，3，3 ′，3 ′-四甲基吲哚羰花青碘化物（作为受体）-和1，1 ′-双十八烷基-3，3，3 ′，3 ′-四甲基吲哚羰花青，4-氯苯磺酸盐（作为供体）-共染的纳米颗粒静脉内施用给小鼠，并使用荧光体内成像仪进行成像。在FRET、供体和受体通道中获得图像的荧光强度，并且通过补偿渗出来定量肿瘤区域中的纳米颗粒动力学。其次，在小鼠的清除的肿瘤组织中，检查纳米颗粒的二维和三维可视化之间的评价性质的差异。简而言之，在荧光标记的番茄凝集素治疗后，将装载有1，1 ′-双十八烷基-3，3，3 ′，3 ′-四甲基吲哚羰花青高氯酸盐（DiI）的纳米颗粒静脉内给予小鼠，以使肿瘤血管可视化。切除的肿瘤组织被清除，并使用激光扫描共聚焦显微镜观察，并重建三维图像。使用二维距离和切片位置的信息，利用毕达哥拉斯定理计算DiI从肿瘤血管行进的三维最小距离。这些成像技术应促进癌症药物输送系统的发展。
In this study, the imaging methods for evaluating the kinetics of nanoparticles as drug delivery systems in tumor tissues were improved in BxPC3 tumor-bearing mice. First, Förster resonance energy transfer (FRET) live imaging was selected to quantitatively evaluate nanoparticle kinetics in the tumor tissue of mice. Briefly, and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine iodide (as an acceptor)–and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt (as a donor)-coloaded nanoparticles were administered intravenously to the mice, and imaging was performed using a fluorescencein vivoimager. The fluorescence intensities of images were acquired in the FRET, donor, and acceptor channels, and the nanoparticle kinetics in the tumor region was quantified by compensating for bleed-through. Second, in the cleared tumor tissue of mice, the difference in evaluation properties between the two- and three-dimensional visualization of the nanoparticles was examined. In brief, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-loaded nanoparticles were intravenously administered to the mice after fluorescently labeled tomato lectin treatment to visualize tumor vessels. Excised tumor tissue was cleared and observed using laser-scanning confocal microscopy, and three-dimensional images were reconstructed. The three-dimensional minimum distances traveled by DiI from the tumor vessels were calculated using information about the two-dimensional distance and the slicing position using the Pythagoras theorem. These imaging techniques should facilitate the development of drug delivery systems for cancer.