Ultrasound beam steering of oxygen nanobubbles for enhanced bladder cancer therapy

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...

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Bibliographic Details
Published in:Scientific reports 2018-02, Vol.8 (1), p.3112-10, Article 3112
Main Authors: Bhandari, Pushpak, Novikova, Gloriia, Goergen, Craig J, Irudayaraj, Joseph
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - chemistry
Bladder cancer
Cancer therapies
Cell Line, Tumor
Cellulose - administration & dosage
Cellulose - chemistry
Disease Models, Animal
Doppler effect
Drug delivery
Drug Delivery Systems - methods
Female
Hypoxia
Mice
Mice, Inbred C57BL
Microbubbles - therapeutic use
Mitomycin - administration & dosage
Mitomycin - chemistry
Mitomycin C
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Oxygen
Oxygen - administration & dosage
Oxygen - chemistry
Random Allocation
Ultrasonic imaging
Ultrasonography - methods
Ultrasound
Urinary bladder
Urinary Bladder Neoplasms - diagnostic imaging
Urinary Bladder Neoplasms - drug therapy
Urothelial carcinoma
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-20363-8