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journal article·2026-02Open access

Precision mRNA Delivery via Ultrasound‐Controlled Release Perfluorocarbon Emulsions: An Innovative Ultrasound Theranostic Strategy with 19 F MRI Feasibility

Haikun Liu, Mark Louis P. Vidallon, Yuyang Song, Aidan P. G. Walsh, Henry Gordon, Shulei Ren, Pengkai Shi, Bangyan Xu, Mitchell J. Moon, Sylvain Trépout, Rico F. Tabor, Alexis I. Bishop, Ulrich Flögel, Karlheinz Peter, Xiaowei Wang

Small· Volume 22· Issue 11
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Abstract

Abstract Messenger RNA (mRNA) therapeutics provide promising opportunities in cardiovascular diseases. However, effective vascular mRNA delivery requires precise delivery, controlled release, and efficient transfection. To address these challenges, the study utilizes phase‐change perfluorocarbon nanodroplets (PFC NDs) as a unique theranostic platform, integrating multimodal imaging with ultrasound‐triggered mRNA release for enhanced vascular transfection. Lipid‐coated PFC NDs are engineered using perfluoro‐crown‐ether (PFCE), perfluorohexane (PFH), and perfluoropentane (PFP) as core materials. These nanodroplets (200–300 nm) are optimized for mRNA loading and cellular uptake, exhibiting strong ultrasound contrast in tissue‐mimicking phantoms and in vivo. Each PFC generated distinct fluorine‐19 magnetic resonance imaging signals, allowing tri‐spectral imaging capabilities. In vitro, PFH and PFP NDs increased enhanced green fluorescent protein mRNA transfection in CHO cells ( p < 0.0001), with ultrasound stimulation further improving efficiency compared to unstimulated controls ( p < 0.05). In vivo ultrasound‐guided activation of PFH NDs resulted in higher mCherry protein expression in murine carotid arteries ( p < 0.05), demonstrating site‐specific gene therapy. This study establishes PFH NDs as an advanced theranostic platform for vascular mRNA delivery, integrating diagnostics and therapeutics into a single system. By leveraging ultrasound‐responsive activation, these nanodroplets overcome existing delivery limitations, offering a new avenue for precision medicine in cardiovascular disease.
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Research context

Nanomaterials

OpenAlex topics: Ultrasound and Hyperthermia Applications · RNA Interference and Gene Delivery · Nanoparticle-Based Drug Delivery

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Molecular Imaging and NanoTherapeutics Laboratory Baker Heart and Diabetes Institute 75 Commercial Road Melbourne VIC 3004 Australia

Centre for Cardiometabolic mRNA Therapy Baker Heart and Diabetes Institute 75 Commercial Road Melbourne VIC 3004 Australia

Department of Cardiometabolic Health University of Melbourne Parkville VIC 3010 Australia

School of Chemistry Monash University Clayton VIC 3800 Australia

Baker Department of Cardiovascular Research Translation and Implementation La Trobe University Bundoora VIC 3086 Australia

Atherothrombosis and Vascular Biology Laboratory Baker Heart and Diabetes Institute 75 Commercial Road Melbourne VIC 3004 Australia

Ramaciotti Centre for Cryo‐electron Microscopy Monash University Clayton VIC 3800 Australia

School of Physics and Astronomy Monash University Clayton VIC 3800 Australia

Institute for Molecular Cardiology Medical Faculty and University Hospital Düsseldorf Heinrich‐Heine‐University Düsseldorf Universitätsstraße 1 40225 Düsseldorf Germany

Cardiovascular Research Institute Düsseldorf (CARID) Medical Faculty and University Hospital Düsseldorf Heinrich‐Heine University Düsseldorf Universitätsstraße 1 40225 Düsseldorf Germany

School of Translational Medicine Monash University Melbourne VIC 3004 Australia

Funding

National Health and Medical Research Council · Deutsche Forschungsgemeinschaft · Baker Heart and Diabetes Institute · National Heart Foundation of Australia · Australian Institute of Nuclear Science and Engineering · Sir Edward 'Weary' Dunlop Medical Research Foundation · Cass Foundation

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