Inhibition of prostate cancer growth using doxorubicin assisted by ultrasound-targeted nanobubble destruction

Abstract

Ultrasound (US)-targeted microbubble destruction has been widely used as an effective drug-delivery system. However, nanobubbles (NBs) have better stability and stronger penetration than microbubbles, and drug delivery assisted by US-targeted NB destruction (UTND) still needs to be investigated. Our aim was to investigate the effect of doxorubicin (DOX) on the inhibition of prostate cancer growth under UTND. Contrast-enhanced US imaging of transplanted PC3 prostate cancer in mice showed that under a combination of 1 W/cm 2 US power and a 100 Hz intermittent pulse with a “5 seconds on, 5 seconds off” mode, NBs with an average size of (485.7±33) nm were effectively destroyed within 15 minutes in the tumor location. PC3 cells and 20 tumor-bearing mice were divided into four groups: a DOX group, a DOX + NB group, a DOX + US group, and a DOX + NB + US group. The cell growth-inhibition rate and DOX concentration of xenografts in the DOX + NB + US group were highest. Based on another control group and these four groups, another 25 tumor-bearing mice were used to observe the treatment effect of nine DOX injections under UTND. The xenografts in the DOX + NB + US group decreased more obviously and had more cellular apoptosis than other groups. Finally, electron microscopy was used to estimate the cavitation effect of NBs under US irradiation in the control group, NB group, US group, and NB + US group. The results of scanning electron microscopy showed that PC3 cells in the DOX + NB + US group had more holes and significantly increased cell-surface folds. Meanwhile, transmission electric microscopy confirmed that more lanthanum nitrate particles entered the parenchymal cells in xenografts in the NB + US group compared with the other groups. This study suggested that UTND technology could be an effective method to promote drugs to function in US-irradiated sites, and the underlying mechanism may be associated with a cavitation effect.

<p>G250 Antigen-Targeting Drug-Loaded Nanobubbles Combined with Ultrasound Targeted Nanobubble Destruction: A Potential Novel Treatment for Renal Cell Carcinoma</p>

“…To ensure reperfusion of the tumor area after NB destruction, the built-in 100-Hz pulse of the therapeutic device was combined with the manual "5 s on, 5 s off" mode. 13 The volume of transplanted tumors in nude mice was recorded on the day treatment started and every 3 days after treatment. After 2 weeks of treatment, all mice were sacrificed, and xenograft tumors were removed.…”

“…Ultrasound can locally release drug-loaded NBs under ultrasound-targeted nanobubble destruction (UTND), which not only increases the local drug concentrations but also reduces toxic and side effects caused by systemic administration and improves antitumor efficacy, maximizing drug efficacy and minimizing toxic and side effects. 13,14 Based on the above research, this study designed G250 antigen-targeting (anti-G250 nanobody-carrying) temsirolimus-loaded nanobubbles (G250-TNBs) to verify the targeting effect of this TDDS on renal cancer cells, to investigate the inhibitory effect of G250-TNBs and UTND on the growth of renal cancer cells in vitro, and to examine the therapeutic effect of G250-TNBs and UTND on RCC xenografts in nude mice in vivo.…”

Carbon Nanotubes-Doxorubicin Conjugates Molecular Dynamics and Bio-inspired Approaches for Clinical Toxicology

“…Doxorubicin (DOX) or hydroxydaunorubicin, is a drug widely used in cancer chemotherapy [1][2][3]. It is an antibiotic of the anthracycline family, being an intercalator of DNA [4].…”

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

“…Previous studies have shown that ultrasound molecular imaging provides new ideas for early diagnosis, treatment and e cient monitoring of prostate cancer due to its real-time dynamic imaging, therapeutic controllability and easy operation [4,5]. However, due to the poor sensitivity and speci city of conventional ultrasound in the diagnosis of prostate cancer, the development of an ultrasound contrast agent with good sensitivity and strong contrast is urgent for current research in prostate cancer ultrasound molecular imaging [6].…”