@article{7054bf43d4304207ae2513ce2e680ad8,
title = "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.",
author = "Pushpak Bhandari and Gloriia Novikova and Goergen, {Craig J.} and Joseph Irudayaraj",
note = "Competing Interests: P.B. and J.I. declare potential financial interests in the future development and commercialization of similar nanomaterials. Office of Technology Commercialization (OTC) of Purdue Research Foundation (PRF) has filed non-provisional patent USSN: 14/873,208 for the technology. The authors would like to acknowledge Dr. Ben Elzey, Dr. Sandra Torregrosa-Allen and Ben Ramsey for their help with tumor xenografting and mice handling, and Evan Phillips for help with ultrasound imaging. We thank Chris Long, John Hamlin, Gnyanesh Gandhe, undergraduate students at Purdue University, for help with the animal experiments and dark-field imaging. The authors acknowledge Dr. Daniel Woods, doctoral student at Purdue University, for his help with ultrasound modeling. Histological processing and immunohistochemistry were performed by Constance J Temm, PhD in the Research Immunohistochemistry Facility of the Indiana University School of Medicine, Department of Pathology and Laboratory Medicine. The authors gratefully acknowledge the help and support from the Purdue University Center for Cancer Research, NIH grant P30 CA023168 and the Jim and Diann Robbers Cancer Research Grant for New Investigators Award (C.J.G). Work was also supported in part by the Indiana Clinical and Translational Sciences Institute, funded in part by Award Number UL1TR001108 from NIH, the TRASK grant from the Purdue Research Foundation and the W.M. Keck Foundation grant.",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41598-018-20363-8",
language = "English (US)",
volume = "8",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Research",
number = "1",
}