Abstract
BackgroundCombining 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.ResultsIn 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.ConclusionsICG-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.
Highlights
Prostate cancer is one of the most common malignancies of the male genitourinary system
Characterization of indocyanine green (ICG)‐paclitaxel nanobubbles group (PTX NBs) The appearances of the ICG-PTX NBs and Blank NBs were observed (Fig. 1a), and the ICG-PTX NBs presented as a pale green emulsion, while the Blank NBs presented as a white emulsion, indicating that ICG was effectively encapsulated in ICG-PTX NBs
ICG-PTX NBs were found to be evenly distributed in size and shape without aggregation (Fig. 1b)
Summary
Prostate cancer is one of the most common malignancies of the male genitourinary system. Near-infrared fluorescence imaging has the advantages of real-time imaging, high sensitivity, no ionizing radiation use and reduced cost It has been extensively used for the early diagnosis and targeted therapy of diseases; due to its strong optical scattering and limited penetration depth, which leads to poor spatial positioning, it has significant limitations in clinical applications [7]. Combining the high penetration depth of pure ultrasound imaging with the high contrast of pure optical imaging, photoacoustic imaging provides tissue imaging with high contrast and resolution, thereby enabling rapid, direct measurements and the tracking of tumour growth and metastasis, as well as real-time imaging and analysis of the obtained data It has great application potential in tumour diagnosis and treatment monitoring [8]. 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
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