Combined Fluorescence and Optoacoustic Imaging for Monitoring Treatments against CT26 Tumors with Photoactivatable Liposomes.
Combined Fluorescence and Optoacoustic Imaging for Monitoring Treatments against CT26 Tumors with Photoactivatable Liposomes.
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荧光和光声成像联合监测光活化脂质体治疗CT26肿瘤
DOI：
10.3390/cancers14010197
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发表时间：
2021-12-31
期刊：
影响因子：
5.2
通讯作者：
Hasan T
中科院分区：
文献类型：
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作者：
Turchin I;Bano S;Kirillin M;Orlova A;Perekatova V;Plekhanov V;Sergeeva E;Kurakina D;Khilov A;Kurnikov A;Subochev P;Shirmanova M;Komarova A;Yuzhakova D;Gavrina A;Mallidi S;Hasan T
提出了一种结合光声（OA）和荧光（FL）成像的新方法，用于在体实时跟踪光敏剂（PS）在治疗区域的动力学和功能性血管效应。使用可光活化的多抑制剂脂质体（PMIL）平台进行的FL监测表明治疗后24小时肿瘤中PS积累的增强。OA监测显示治疗后肿瘤血管结构的改变，这与组织学数据非常一致，组织学数据显示PMIL治疗组小鼠的肿瘤百分比比未治疗组高5倍。新开发的多模式成像系统结合了光栅扫描光声（OA）显微镜和荧光（FL）宽场成像，用于以38/50 μm的轴向/横向分辨率表征肿瘤血管结构，并评估新型治疗诊断剂治疗期间的光敏剂荧光动力学。本文设计了一种多功能光活化多抑制剂脂质体（PMILs）纳米平台，其双层中含有临床批准的光敏剂苯并卟啉衍生物（BPD），其内核中含有拓扑异构酶I抑制剂伊立替康（IRI），用于协同治疗效果。优化的PMIL是阴离子型的，流体动力学直径为131.6 ± 2.1 nm，多分散指数（PDI）为0.05 ± 0.01，zeta电位在−14.9 ± 1.04至−16.9 ± 0.92 mV之间。在体内研究中，对患有CT 26肿瘤的BALB/c小鼠进行研究以评估PMIL的治疗功效。PMIL对肿瘤生长的最佳抑制效果为97%，而含BPD-PC的脂质体（帕尔斯）的抑制效果为81%，含IRI的脂质体（L-[IRI]）单独给药的抑制效果为50%。这证实了在由NIR光触发PMIL时肿瘤细胞内IRI的释放，这另外通过FL监测来说明，表明在治疗后24小时内由PDT引发的肿瘤中药物积累的增强。OA监测显示，与BPD-PC或IRI治疗的小鼠相比，PMIL治疗的小鼠中肿瘤血管结构的变化最大。组织学数据进一步证实了结果，组织学数据也显示与对照组相比，PMIL处理的小鼠中的肿瘤百分比高5倍。总体而言，这些结果表明，多功能PMIL同时递送PDT和化疗剂沿着OA和FL多模态成像提供了一个有效和个性化的图像引导平台，以改善癌症治疗结果。
A new approach of combined optoacoustic (OA) and fluorescence (FL) imaging for in vivo real-time tracing photosensitizer (PS) kinetics and functional vascular effects in the treated area was developed. FL monitoring using a photoactivatable multi-inhibitor liposomal (PMILs) platform, demonstrates enhancement of PS accumulation in tumor, 24 h post-treatment. OA monitoring revealed the alterations of the tumor vasculature structure after treatment, which is in good agreement with the histological data that shows five times higher percentage of hemorrhages in PMIL treated mice compared to the untreated group. The newly developed multimodal imaging system combining raster-scan optoacoustic (OA) microscopy and fluorescence (FL) wide-field imaging was used for characterizing the tumor vascular structure with 38/50 μm axial/transverse resolution and assessment of photosensitizer fluorescence kinetics during treatment with novel theranostic agents. A multifunctional photoactivatable multi-inhibitor liposomal (PMILs) nano platform was engineered here, containing a clinically approved photosensitizer, Benzoporphyrin derivative (BPD) in the bilayer, and topoisomerase I inhibitor, Irinotecan (IRI) in its inner core, for a synergetic therapeutic impact. The optimized PMIL was anionic, with the hydrodynamic diameter of 131.6 ± 2.1 nm and polydispersity index (PDI) of 0.05 ± 0.01, and the zeta potential between −14.9 ± 1.04 to −16.9 ± 0.92 mV. In the in vivo studies on BALB/c mice with CT26 tumors were performed to evaluate PMILs’ therapeutic efficacy. PMILs demonstrated the best inhibitory effect of 97% on tumor growth compared to the treatment with BPD-PC containing liposomes (PALs), 81%, or IRI containing liposomes (L-[IRI]) alone, 50%. This confirms the release of IRI within the tumor cells upon PMILs triggering by NIR light, which is additionally illustrated by FL monitoring demonstrating enhancement of drug accumulation in tumor initiated by PDT in 24 h after the treatment. OA monitoring revealed the largest alterations of the tumor vascular structure in the PMILs treated mice as compared to BPD-PC or IRI treated mice. The results were further corroborated with histological data that also showed a 5-fold higher percentage of hemorrhages in PMIL treated mice compared to the control groups. Overall, these results suggest that multifunctional PMILs simultaneously delivering PDT and chemotherapy agents along with OA and FL multi-modal imaging offers an efficient and personalized image-guided platform to improve cancer treatment outcomes.