Department of Ultrasound, Southwest Hospital, Army Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
State Key Laboratory Of Silkworm Genome Biology, Southwest University, Beibei District, Chongqing, China.
J Nanobiotechnology. 2020 Sep 3;18(1):121. doi: 10.1186/s12951-020-00650-1.
Combining ultrasound imaging with photoacoustic imaging provides tissue imaging with high contrast and resolution, thereby enabling rapid, direct measurements and the tracking of tumour growth and metastasis. Moreover, ultrasound-targeted nanobubble destruction (UTND) provides an effective way to deliver drugs, effectively increasing the content of the drug in the tumour area and reducing potential side effects, thereby successfully contributing to the treatment of tumours.
In this study, we prepared multifunctional nanobubbles (NBs) carrying indocyanine green (ICG) and paclitaxel (PTX) (ICG-PTX NBs) and studied their applications in ultrasound imaging of prostate cancer as well as their therapeutic effects on prostate cancer when combined with UTND. ICG-PTX NBs were prepared by the mechanical oscillation method. The particle size and zeta potential of the ICG-PTX NBs were 469.5 ± 32.87 nm and - 21.70 ± 1.22 mV, respectively. The encapsulation efficiency and drug loading efficiency of ICG were 68% and 2.52%, respectively. In vitro imaging experiments showed that ICG-PTX NBs were highly amenable to multimodal imaging, including ultrasound, photoacoustic and fluorescence imaging, and the imaging effect was positively correlated with their concentration. The imaging effects of tumour xenografts also indicated that ICG-PTX NBs were of good use for multimodal imaging. In experiments testing the growth of PC-3 cells in vitro and tumour xenografts in vivo, the ICG-PTX NBs + US group showed more significant inhibition of cell proliferation and the promotion of cell apoptosis compared to the other groups (P < 0.05). Blood biochemical analysis of the six groups showed that the levels of aspartate aminotransferase (AST), phenylalanine aminotransferase (ALT), serum creatinine (CRE) and blood urea nitrogen (BUN) in the ICG-PTX NBs and the ICG-PTX NBs + US groups were significantly lower than those in the PTX group (P < 0.05). Moreover, H&E staining of tissue sections from vital organs showed no obvious abnormalities in the ICG-PTX NBs and the ICG-PTX NBs + US groups.
ICG-PTX NBs can be used as a non-invasive, pro-apoptotic contrast agent that can achieve multimodal imaging, including ultrasound, fluorescence and photoacoustic imaging, and can succeed in the local treatment of prostate cancer providing a potential novel method for integrated research on prostate cancer diagnosis and treatment.
将超声成像与光声成象结合使用，可为组织成像提供高对比度和分辨率，从而能够快速、直接地测量并跟踪肿瘤的生长和转移。此外，超声靶向纳米泡破坏（UTND）为药物输送提供了一种有效途径，可有效增加肿瘤区域的药物含量，降低潜在的副作用，从而成功有助于肿瘤的治疗。
在这项研究中，我们制备了携带吲哚菁绿（ICG）和紫杉醇（PTX）的多功能纳米泡（NBs）（ICG-PTX NBs），并研究了它们在前列腺癌超声成像中的应用，以及与 UTND 结合时对前列腺癌的治疗效果。ICG-PTX NBs 通过机械振荡法制备。ICG-PTX NBs 的粒径和 Zeta 电位分别为 469.5±32.87nm 和-21.70±1.22mV。ICG 的包封效率和载药效率分别为 68％和 2.52％。体外成像实验表明，ICG-PTX NBs 非常适合于多模式成像，包括超声、光声和荧光成像，并且成像效果与它们的浓度呈正相关。肿瘤异种移植的成像效果也表明，ICG-PTX NBs 非常适合于多模式成像。在体外检测 PC-3 细胞生长和体内肿瘤异种移植的实验中，与其他组相比，ICG-PTX NBs+US 组显示出更明显的抑制细胞增殖和促进细胞凋亡的作用（P<0.05）。六组的血液生化分析表明，ICG-PTX NBs 和 ICG-PTX NBs+US 组的天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、血清肌酐（CRE）和血尿素氮（BUN）水平明显低于 PTX 组（P<0.05）。此外，重要器官组织切片的 H&E 染色显示，ICG-PTX NBs 和 ICG-PTX NBs+US 组无明显异常。
ICG-PTX NBs 可用作非侵入性促凋亡造影剂，可实现多模式成像，包括超声、荧光和光声成像，并能成功地进行局部前列腺癌治疗，为前列腺癌的诊断和治疗综合研究提供了一种新的潜在方法。
