State Key Laboratory of Modern Optical Instrumentations, Centre for Optical and Electromagnetic Research; JORCEP (Sino-Swedish Joint Research Center of Photonics), Zhejiang University, Hangzhou, 310058, China.
Department of Urology, Sir Run-Run Shaw Hospital College of Medicine, Zhejiang University, Hangzhou 310016, China.
Theranostics. 2019 Aug 9;9(19):5706-5719. doi: 10.7150/thno.31332. eCollection 2019.
Cerebrovascular diseases, together with malignancies, still pose a huge threat to human health nowadays. With the advantages of its high spatial resolution and large penetration depth, fluorescence bioimaging in the second near-infrared spectral region (NIR-II, 900-1700 nm) and its related imaging-guided therapy based on biocompatible fluorescence dyes have become a promising theranostics method. The biocompatibility of IR-820 we used in NIR-II fluorescence bioimaging was verified by long-term observation. The model of the mouse with a cranial window, the mouse model of middle cerebral artery occlusion (MCAO) and a subcutaneous xenograft mouse model of bladder tumor were established. NIR-II fluorescence cerebrovascular functional imaging was carried out by IR-820 assisted NIR-II fluorescence microscopy. Bladder tumor was treated by NIR-II fluorescence imaging-guided photothermal therapy. We have found that IR-820 has considerable NIR-II fluorescence intensity, and shows increased brightness in serum than in water. Herein, we achieved real time and cerebrovascular functional imaging of mice with high spatial resolution and large penetration depth, based on IR-820 assisted NIR-II fluorescence microscopy. In addition, IR-820 was successfully employed for NIR-II fluorescence imaging and photothermal therapy of tumor , and the subcutaneous tumors were inhibited obviously or eradicated completely. Due to the considerable fluorescence intensity in NIR-II spectral region and the good photothermal effect, biocompatible and excretable IR-820 holds great potentials for functional angiography and cancer theranostics in clinical practice.
脑血管疾病与恶性肿瘤一样，目前仍然对人类健康构成巨大威胁。具有高空间分辨率和大穿透深度优势的近红外二区（NIR-II，900-1700nm）荧光生物成像及其基于生物相容性荧光染料的相关成像引导治疗已成为一种很有前途的诊断和治疗方法。我们在 NIR-II 荧光生物成像中使用的 IR-820 的生物相容性已通过长期观察得到验证。建立了带有颅窗的小鼠模型、大脑中动脉阻塞（MCAO）的小鼠模型和膀胱癌皮下异种移植小鼠模型。通过 IR-820 辅助的近红外二区荧光显微镜进行 NIR-II 荧光脑血管功能成像。通过 NIR-II 荧光成像引导光热治疗来治疗膀胱癌。我们发现 IR-820 具有相当强的近红外二区荧光强度，并且在血清中的亮度比在水中的亮度增加。在此，我们基于 IR-820 辅助的近红外二区荧光显微镜，实现了对小鼠的实时、高空间分辨率和大穿透深度的脑血管功能成像。此外，IR-820 成功地用于肿瘤的 NIR-II 荧光成像和光热治疗，并且皮下肿瘤被明显抑制或完全消除。由于在近红外二区光谱区具有相当强的荧光强度和良好的光热效应，生物相容性和可排泄的 IR-820 在临床实践中具有用于功能血管造影和癌症诊断与治疗的巨大潜力。
