Theranostics 2015; 5(1):97-109. doi:10.7150/thno.10298

Research Paper

Theranostic mRNA-loaded Microbubbles in the Lymphatics of Dogs: Implications for Drug Delivery

Heleen Dewitte1*, Katrien Vanderperren2*, Hendrik Haers2, Emmelie Stock2, Luc Duchateau3, Myriam Hesta4, Jimmy H. Saunders2, Stefaan C. De Smedt1✉, Ine Lentacker1

1. Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent, Belgium;
2. Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium;
3. Department of Comparative Physiology and Biometrics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium;
4. Department of Animal Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
* both first authors contributed equally to this work.

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Citation:
Dewitte H, Vanderperren K, Haers H, Stock E, Duchateau L, Hesta M, Saunders JH, De Smedt SC, Lentacker I. Theranostic mRNA-loaded Microbubbles in the Lymphatics of Dogs: Implications for Drug Delivery. Theranostics 2015; 5(1):97-109. doi:10.7150/thno.10298. Available from http://www.thno.org/v05p0097.htm

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Abstract

Microbubbles have shown potential as intralymphatic ultrasound contrast agents while nanoparticle-loaded microbubbles are increasingly investigated for ultrasound-triggered drug and gene delivery. To explore whether mRNA-nanoparticle loaded microbubbles could serve as theranostics for detection of and mRNA transfer to the lymph nodes, we investigate the behavior of unloaded and mRNA-loaded microbubbles using contrast-enhanced ultrasound imaging after subcutaneous injection in dogs. Our results indicate that both types of microbubbles are equally capable of rapidly entering the lymph vessels and nodes upon injection, and novel, valuable and detailed information on the lymphatic structure in the animals could be obtained. Furthermore, additional observations were made regarding the dynamics of microbubble lymph node uptake. Importantly, neither the microbubble migration distance within the lymphatics, nor the observed contrast signal intensity was influenced by mRNA-loading. Although further optimization of acoustic parameters will be needed, this could represent a first step towards ultrasound-guided, ultrasound-triggered intranodal mRNA delivery using these theranostic microbubbles.

Keywords: Contrast-enhanced ultrasound imaging, mRNA, microbubbles, mRNA-loaded microbubbles, dogs, lymph nodes.