title: Theranostic mRNA-loaded microbubbles in the lymphatics of dogs: implications for drug delivery.
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.
authors.affiliation: 1. Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent, Belgium;
authors.forename: Heleen
authors.initials: H
authors.lastname: Dewitte
authors.affiliation: 2. Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium;
authors.forename: Katrien
authors.initials: K
authors.lastname: Vanderperren
authors.affiliation: 2. Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium;
authors.forename: Hendrik
authors.initials: H
authors.lastname: Haers
authors.affiliation: 2. Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium;
authors.forename: Emmelie
authors.initials: E
authors.lastname: Stock
authors.affiliation: 3. Department of Comparative Physiology and Biometrics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium;
authors.forename: Luc
authors.initials: L
authors.lastname: Duchateau
authors.affiliation: 4. Department of Animal Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Hesta
authors.affiliation: 2. Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium;
authors.forename: Jimmy H
authors.initials: JH
authors.lastname: Saunders
authors.affiliation: 1. Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent, Belgium;
authors.forename: Stefaan C
authors.initials: SC
authors.lastname: De Smedt
authors.affiliation: 1. Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent, Belgium;
authors.forename: Ine
authors.initials: I
authors.lastname: Lentacker
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000378:metabolism; D004283:Dog Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism*; D004285:Dogs; D005260:Female; D018014:Gene Transfer Techniques; D008206:Lymphatic Diseases / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000662:veterinary*; D008297:Male; D045423:Microbubbles / Q000627:therapeutic use*; D053758:Nanoparticles / Q000378:metabolism; D012333:RNA, Messenger / Q000493:pharmacokinetics*; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D012333:RNA, Messenger
keywords: Contrast-enhanced ultrasound imaging; dogs; lymph nodes.; mRNA; mRNA-loaded microbubbles; microbubbles