Targeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer
Targeted Nanobubbles Carrying Indocyanine Green for Ultrasound, Photoacoustic and Fluorescence Imaging of Prostate Cancer
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DOI：
10.2147/ijn.s243548
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发表时间：
2020-06
影响因子：
8
通讯作者：
Yixuan Wang;Minmin Lan;Daijia Shen;Kejing Fang;Lianhua Zhu;Yu Liu;Lan Hao;Pan Li
中科院分区：
文献类型：
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作者：
Yixuan Wang;Minmin Lan;Daijia Shen;Kejing Fang;Lianhua Zhu;Yu Liu;Lan Hao;Pan Li
目的构建以前列腺特异性膜抗原（PSMA）为靶点，负载吲哚菁绿（ICG）的纳米气泡（NBs）用于前列腺癌的超声、光声和荧光多模态成像。方法采用机械振荡法制备ICG负载光声NBs （ICG NBs）。然后，利用生物素-亲和素方法将psma结合肽连接到ICG nb表面，制成靶向光声nb，即PSMAP/ICG nb。检测了它们的粒径、zeta电位、体外超声、光声和荧光成像。采用共聚焦激光扫描显微镜和流式细胞术检测PSMAP/ICG NBs与psma阳性LNCaP细胞、C4-2细胞和psma阴性PC-3细胞的结合能力。比较PSMAP/ICG NBs与ICG NBs在裸鼠肿瘤移植中的多模态成像效果。结果制备的PSMAP/ICG纳米粒子粒径约为457.7 nm， zeta电位约为- 23.5 mV。激光共聚焦扫描显微镜和流式细胞术均证实PSMAP/ICG NBs能特异性结合LNCaP和C4-2细胞，但很少结合PC-3细胞。PSMAP/ICG NBs体外超声、光声和荧光成像强度与其浓度呈正相关。PSMAP/ICG NBs在LNCaP和C4-2异种肿瘤中的超声和光声成像效果较PC-3异种肿瘤明显增强，超声增强时间明显延长，光声信号强度明显增强（P < 0.05）。荧光成像显示PSMAP/ICG NBs可在LNCaP和C4-2肿瘤移植物中积累较长时间。结论本研究制备的靶向光声纳米泡能特异性结合psma阳性前列腺癌细胞，并能增强psma阳性肿瘤异种移植物的超声、光声和荧光成像。光声成像可以直观地显示肿瘤区域红色光声信号的强弱，为靶向分子成像提供更直观的成像方式。本研究提出了一种潜在的多模态造影剂，用于准确诊断和评估前列腺癌。
Objective To construct prostate-specific membrane antigen (PSMA)-targeting, indocyanine green (ICG)-loaded nanobubbles (NBs) for multimodal (ultrasound, photoacoustic and fluorescence) imaging of prostate cancer. Methods The mechanical oscillation method was used to prepare ICG-loaded photoacoustic NBs (ICG NBs). Then, PSMA-binding peptides were connected to the surface of ICG NBs using the biotin–avidin method to make targeted photoacoustic NBs, namely, PSMAP/ICG NBs. Their particle sizes, zeta potentials, and in vitro ultrasound, photoacoustic and fluorescence imaging were examined. Confocal laser scanning microscopy and flow cytometry were used to detect the binding ability of the PSMAP/ICG NBs to PSMA-positive LNCaP cells, C4-2 cells, and PSMA-negative PC-3 cells. The multimodal imaging effects of PSMAP/ICG NBs and ICG NBs were compared in nude mouse tumor xenografts. Results The particle size of the PSMAP/ICG NBs was approximately 457.7 nm, and the zeta potential was approximately −23.5 mV. Both confocal laser scanning microscopy and flow cytometry confirmed that the PSMAP/ICG NBs could specifically bind to both LNCaP and C4-2 cells, but they rarely bound to PC-3 cells. The ultrasound, photoacoustic and fluorescence imaging intensities of the PSMAP/ICG NBs in vitro positively correlated with their concentrations. The ultrasound and photoacoustic imaging effects of the PSMAP/ICG NBs in LNCaP and C4-2 tumor xenografts were significantly enhanced compared with those in PC-3 tumor xenografts, which were characterized by a significantly increased duration of ultrasound enhancement and heightened photoacoustic signal intensity (P < 0.05). Fluorescence imaging showed that PSMAP/ICG NBs could accumulate in LNCaP and C4-2 tumor xenografts for a relatively long period. Conclusion The targeted photoacoustic nanobubbles prepared in this study can specifically bind to PSMA-positive prostate cancer cells and have the ability to enhance ultrasound, photoacoustic and fluorescence imaging of PSMA-positive tumor xenografts. Photoacoustic imaging could visually display the intensity of the red photoacoustic signal in the tumor region, providing a more intuitive imaging modality for targeted molecular imaging. This study presents a potential multimodal contrast agent for the accurate diagnosis and assessment of prostate cancer.