Multifunctional Nanobubbles Carrying Indocyanine Green and Paclitaxel for Molecular Imaging and Treatment of Prostate Cancer

Abstract

Background: Combining ultrasound imaging with photoacoustic imaging provides tissue imaging with high contrast and high resolution, thereby enabling rapid and direct measurement and tracking of tumor growth and metastasis. At the same time, ultrasound targeted nanobubble destruction (UTND) provides an effective way to drug accumulation; effectively increasing the content of the drug in the tumor area and reducing potential side effects, thereby contributing effectively to the treatment of the tumors.Result: In this study, we prepared multifunctional nanobubbles (NBs) carrying indocyanine green (ICG) and paclitaxel (PTX) (ICG-PTX NBs), and study their application in ultrasound imaging of prostate cancer as well as their therapeutic effect on prostate cancer when combined with ultrasound targeted nanobubble destruction (UTND). ICG-PTX NBs were prepared by mechanical oscillation method. Their particle size and Zeta potential of ICG-PTX NBs were 469.5±32.87 nm and -21.70±1.222 mV, respectively. The encapsulation efficiency and drug loading efficiency of ICG were 68% and 6.2%, 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 is positively correlated with their concentration. The imaging effect of tumor 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 tumor xenografts in vivo, the ICG-PTX NBs+US group showed more significant inhibition of cell proliferation and 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 group and the ICG-PTX NBs+US group were significantly lower than those in the PTX group (P < 0.05). Moreover, H&E staining of tissue sections from vital organ showed no obvious abnormalities in the ICG-PTX NBs group and the ICG-PTX NBs+US group.Conclusions: ICG-PTX NBs can be used as a non-invasive, pro-apoptotic contrast agent for both diagnosis and treatment that can achieve enhanced imaging, effective inhibition and killing of prostate cancer under the guidance of multimodal imaging including ultrasound, fluorescence and photoacoustic imaging.

Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma

“…Also, PTX was capable of activating caspase-3 (the effector of apoptosis pathways) and reducing Bcl-2 expression (the anti-apoptotic protein) to repress glioma cell apoptosis [ 34 ], which was partially consistent with our findings. Moreover, nanobubbles carrying ICG and PTX cause a more significant promotion of prostate cancer cell apoptosis compared to treatments with PTX or ICG alone [ 35 ]. More importantly, NRP-1-targeted RGE-conjugated EVs have been documented to facilitate diagnosis and therapy of glioma, both in vitro and in vivo [ 16 ], which is in line with our finding that active targeting of ICG/PTX@RGE-EV in glioma was achieved by RGE-peptide specific targeting of NRP-1.…”