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Theranostic mRNA-loaded microbubbles in the lymphatics of dogs: implications for drug delivery

Heleen Dewitte (UGent) , Katrien Vanderperren (UGent) , Hendrik Haers (UGent) , Emmelie Stock (UGent) , Luc Duchateau (UGent) , Myriam Hesta (UGent) , Jimmy Saunders (UGent) , Stefaan De Smedt (UGent) and Ine Lentacker (UGent)
(2015) THERANOSTICS. 5(1). p.97-109
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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
mRNA, Contrast-enhanced ultrasound imaging, microbubbles, mRNA-loaded microbubbles, dogs, lymph nodes, CONTRAST-ENHANCED ULTRASOUND, SENTINEL NODE IDENTIFICATION, DENDRITIC CELLS, IN-VIVO, CATIONIC MICROBUBBLES, CANCER-IMMUNOTHERAPY, BREAST-CANCER, PHAGOCYTOSIS, TRANSFECTION, PHYSIOLOGY

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Chicago
Dewitte, Heleen, Katrien Vanderperren, Hendrik Haers, Emmelie Stock, Luc Duchateau, Myriam Hesta, Jimmy Saunders, Stefaan De Smedt, and Ine Lentacker. 2015. “Theranostic mRNA-loaded Microbubbles in the Lymphatics of Dogs: Implications for Drug Delivery.” Theranostics 5 (1): 97–109.
APA
Dewitte, H., Vanderperren, K., Haers, H., Stock, E., Duchateau, L., Hesta, M., Saunders, J., et al. (2015). Theranostic mRNA-loaded microbubbles in the lymphatics of dogs: implications for drug delivery. THERANOSTICS, 5(1), 97–109.
Vancouver
1.
Dewitte H, Vanderperren K, Haers H, Stock E, Duchateau L, Hesta M, et al. Theranostic mRNA-loaded microbubbles in the lymphatics of dogs: implications for drug delivery. THERANOSTICS. 2015;5(1):97–109.
MLA
Dewitte, Heleen, Katrien Vanderperren, Hendrik Haers, et al. “Theranostic mRNA-loaded Microbubbles in the Lymphatics of Dogs: Implications for Drug Delivery.” THERANOSTICS 5.1 (2015): 97–109. Print.
@article{5835292,
  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.},
  author       = {Dewitte, Heleen and Vanderperren, Katrien and Haers, Hendrik and Stock, Emmelie and Duchateau, Luc and Hesta, Myriam and Saunders, Jimmy and De Smedt, Stefaan and Lentacker, Ine},
  issn         = {1838-7640},
  journal      = {THERANOSTICS},
  language     = {eng},
  number       = {1},
  pages        = {97--109},
  title        = {Theranostic mRNA-loaded microbubbles in the lymphatics of dogs: implications for drug delivery},
  url          = {http://dx.doi.org/10.7150/thno.10298},
  volume       = {5},
  year         = {2015},
}

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