Ultrasound beam steering of oxygen nanobubbles for enhanced bladder cancer therapy

Abstract

New intravesical treatment approaches for bladder cancer are needed as currently approved treatments show several side effects and high tumor recurrence rate. Our study used MB49 murine urothelial carcinoma model to evaluate oxygen encapsulated cellulosic nanobubbles as a novel agent for imaging and ultrasound guided drug delivery. In this study, we show that oxygen nanobubbles (ONB) can be propelled (up to 40 mm/s) and precisely guided in vivo to the tumor by an ultrasound beam. Nanobubble velocity can be controlled by altering the power of the ultrasound Doppler beam, while nanobubble direction can be adjusted to different desired angles by altering the angle of the beam. Precise ultrasound beam steering of oxygen nanobubbles was shown to enhance the efficacy of mitomycin-C, resulting in significantly lower tumor progression rates while using a 50% lower concentration of chemotherapeutic drug. Further, dark field imaging was utilized to visualize and quantify the ONB ex vivo. ONBs were found to localize up to 500 µm inside the tumor using beam steering. These results demonstrate the potential of an oxygen nanobubble drug encapsulated system to become a promising strategy for targeted drug delivery because of its multimodal (imaging and oxygen delivery) and multifunctional (targeting and hypoxia programming) properties.

Nanoscale Drug Delivery Systems: From Medicine to Agriculture

“…Other areas within agriculture that could benefit from nano-encapsulation approaches include plant breeding (Kim et al, 2015), plant nutrition (Rai et al, 2015), growth promotion (Siddiqui and Al-Whaibi, 2015), disease control (Nuruzzaman et al, 2016), and post-harvest quality control (Yadollahi et al, 2010) to name a few. Conversely, agricultural materials such as cellulose (Bhandari et al, 2017(Bhandari et al, , 2018 and chitosan (Cai and Lapitsky, 2019) have been used as base materials to develop drug delivery systems.…”

Hydrogel Biomaterials for Application in Ocular Drug Delivery

“…An example is the use of oxygen nanobubbles used for the delivery of mitomycin-C. The nanobubbles system was capable of lower tumor progression rates with a 50% lower drug concentration (Bhandari et al, 2018).…”

Nano drug delivery systems in upper gastrointestinal cancer therapy

“…These carriers can transport drugs in a variety of ways [85]. Other classes of NPs have been designed to deliver adjuvants such as oxygen to mitigate cancer hypoxia to increase the effectiveness of successive therapies [86][87][88]. Despite their advantages, the application of most polymeric NPs is still immature due to widely unknown cellular interactions, low solubility in non-acidic milieu and poorly conceived methods for large scale production.…”