Nanoscaled ultrasound contrast agents for enhanced sonothrombolysis

Brüßler, Jana; Strehlow, Boris; Becker, Andreas; Schubert, Rolf; Schümmelfeder, J.; Nimsky, Christopher; Bakowsky, Udo

doi:10.1016/j.colsurfb.2018.09.037

Cited by 14 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequently it has been found that these liposomes protect rt-PA against degradation by plasminogen activator inhibitor 1, while achieving equivalent thrombolytic efficacy relative to rt-PA, Definity and intermittent 220 kHz CW ultrasound (Shekhar et al 2019). Promising agents, including a nanoscale (<100 nm) contrast agent (Brüssler et al 2018) and magnetically targeted microbubbles (De Saint Victor et al 2019), have also exhibited enhanced rt-PA thrombolysis in vitro. All of these investigators noted that in the absence of rt-PA, the combination of ultrasound and microbubbles did not degrade the fibrin network.…”

Section: Mechanisms Agents and Approachesmentioning

confidence: 99%

Ultrasound-Responsive Cavitation Nuclei for Therapy and Drug Delivery

Kooiman

Roovers

Langeveld

et al. 2020

Ultrasound in Medicine & Biology

247

187

View full text Add to dashboard Cite

Therapeutic ultrasound strategies that harness the mechanical activity of cavitation nuclei for beneficial tissue bio-effects are actively under development. The mechanical oscillations of circulating microbubbles, the most widely investigated cavitation nuclei, which may also encapsulate or shield a therapeutic agent in the bloodstream, trigger and promote localized uptake. Oscillating microbubbles can create stresses either on nearby tissue or in surrounding fluid to enhance drug penetration and efficacy in the brain, spinal cord, vasculature, immune system, biofilm or tumors. This review summarizes recent investigations that have elucidated interactions of ultrasound and cavitation nuclei with cells, the treatment of tumors, immunotherapy, the bloodÀbrain and bloodÀspinal cord barriers, sonothrombolysis, cardiovascular drug delivery and sonobactericide. In particular, an overview of salient ultrasound features, drug delivery vehicles, therapeutic transport routes and pre-clinical and clinical studies is provided. Successful implementation of ultrasound and cavitation nuclei-mediated drug delivery has the potential to change the way drugs are administered systemically, resulting in more effective therapeutics and less-invasive treatments.

show abstract

Section: Mechanisms Agents and Approachesmentioning

confidence: 99%

Ultrasound-Responsive Cavitation Nuclei for Therapy and Drug Delivery

Kooiman

Roovers

Langeveld

et al. 2020

Ultrasound in Medicine & Biology

247

187

View full text Add to dashboard Cite

show abstract

“…Nanodroplets (NDs) are an ultrasound contrast agent, which has recently been applied not only for enhanced ultrasound imaging, but for enhanced drug delivery and more recently, sonothrombolysis of retracted clots [20][21][22][23][24] . Upon insonation with sufficient PNPs, nanodroplets are able to transition from liquid droplets to gas-filled bubbles, which then have similar acoustic properties and behaviors as MBs.…”

Section: Nanodroplet-mediated Sonothrombolysismentioning

confidence: 99%

“…For ND-mediated sonothrombolysis, typical studies use an external HIFU device for these excitations in order to activate the droplets [22][23][24] . Although initial studies are promising, it requires the PNPs of 3-5 MPa to activate the ND, which exceeds the safety limit for ultrasound imaging and causes concerns for clinical translation.…”

Section: Nanodroplet-mediated Sonothrombolysismentioning

confidence: 99%

Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

Goel

Zhang

et al. 2021

Microsyst Nanoeng

View full text Add to dashboard Cite

One major challenge in current microbubble (MB) and tissue plasminogen activator (tPA)-mediated sonothrombolysis techniques is effectively treating retracted blood clots, owing to the high density and low porosity of retracted clots. Nanodroplets (NDs) have the potential to enhance retracted clot lysis owing to their small size and ability to penetrate into retracted clots to enhance drug delivery. For the first time, we demonstrate that a sub-megahertz, forward-viewing intravascular (FVI) transducer can be used for ND-mediated sonothrombolysis, in vitro. In this study, we determined the minimum peak negative pressure to induce cavitation with low-boiling point phase change nanodroplets and clot lysis. We then compared nanodroplet mediated sonothrombolysis to MB and tPA mediate techniques. The clot lysis as a percent mass decrease in retracted clots was 9 ± 8%, 9 ± 5%, 16 ± 5%, 14 ± 9%, 17 ± 9%, 30 ± 8%, and 40 ± 9% for the control group, tPA alone, tPA + US, MB + US, MB + tPA + US, ND + US, and ND + tPA + US groups, respectively. In retracted blood clots, combined ND- and tPA-mediated sonothrombolysis was able to significantly enhance retracted clot lysis compared with traditional MB and tPA-mediated sonothrombolysis techniques. Combined nanodroplet with tPA-mediated sonothrombolysis may provide a feasible strategy for safely treating retracted clots.

show abstract

“…It has been observed elsewhere that echogenicity is based on PEG chain regime on the vesicle. [ 26,36 ]…”

Section: Resultsmentioning

confidence: 99%

Development and Characterization of Ultrasound Activated Lipopolyplexes for Enhanced Transfection by Low Frequency Ultrasound in In Vitro Tumor Model

Shah

Tariq

Engelhardt

et al. 2020

Macromolecular Bioscience

Self Cite

View full text Add to dashboard Cite

This work focuses on the development of ultrasound contrast vesicles for ultrasound‐mediated enhanced transfection of nucleic acids in the cancer cells and projects its application as a tool for diagnostic imaging. The ultrasound contrast vesicles are stable, anionic, nanoscaled vesicles with ultrasound contrast equivalent to the commercially available SonoVue. These anionic lipid vesicles establish electrostatic interaction with cationic polyplexes based on linear polyethylenimine (22kDa) forming lipopolyplexes with ultrasound contrast. The lipopolyplexes are characterized regarding shape, size, and zeta potential. When exposed to low frequency ultrasound, these carriers show elevated transfection efficiency and reduced cytotoxicity. The effect of post‐transfection ultrasound on cellular uptake of lipopolyplexes is also evaluated. An analogous transfection is also observed in the tumor mimicking multicellular 3D spheroid culture of ovarian cancer cells. The emergence of tumor imaging and enhanced gene delivery by medical ultrasound, a noninvasive imaging modality, is considered paving the way for efficient theranostic gene therapy.

show abstract

Nanoscaled ultrasound contrast agents for enhanced sonothrombolysis

Cited by 14 publications

References 28 publications

Ultrasound-Responsive Cavitation Nuclei for Therapy and Drug Delivery

Ultrasound-Responsive Cavitation Nuclei for Therapy and Drug Delivery

Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots

Development and Characterization of Ultrasound Activated Lipopolyplexes for Enhanced Transfection by Low Frequency Ultrasound in In Vitro Tumor Model

Contact Info

Product

Resources

About