The Influence of Nanobubble Size and Stability on Ultrasound Enhanced Drug Delivery

Batchelor, Damien V. B.; Armistead, Fern J.; Ingram, Nicola; Peyman, Sally A.; McLaughlan, James R.; Coletta, P. Louise; Evans, Stephen D.

doi:10.1021/acs.langmuir.2c02303

Cited by 24 publications

(13 citation statements)

References 61 publications

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“…Tethering of the MB sample after HIFU treatment led to a shift of ∼12 Hz, in which the increase in magnitude again can be attributed to removal of gas-filled MBs from the sample. It should be noted that MB samples likely also contain a proportion of submicrometer bubbles (i.e., nanobubbles) ,, that would also be able to interact with the SLB using the cDNA tethers. However, our recent work has shown that the HIFU treatment is also capable of inducing NB destruction …”

Section: Resultsmentioning

confidence: 99%

“…It should be noted that MB samples likely also contain a proportion of submicrometer bubbles (i.e., nanobubbles) ,, that would also be able to interact with the SLB using the cDNA tethers. However, our recent work has shown that the HIFU treatment is also capable of inducing NB destruction …”

Section: Resultsmentioning

confidence: 99%

“…However, our recent work has shown that the HIFU treatment is also capable of inducing NB destruction. 34 …”

Section: Resultsmentioning

confidence: 99%

“…However, our recent work has shown that the HIFU treatment is also capable of inducing NB destruction. 34 Interestingly, dissipation data showed the reverse trend in which MBs only had a reduced dissipation (∼4.5 × 10 −6 ) than that of MBs + HIFU (∼6.5 × 10 −6 ). There are multiple factors that can influence the dissipation of our system, which may lead to changes in dissipation between MBs or liposomes tethered to the SLB.…”

Section: Mb−bilayer Interactionsmentioning

confidence: 95%

“…A 30 μL volume of sample was introduced into a 50 μm depth chamber on a glass slide, and MBs were allowed to rise for 5 min to ensure they were all in the same focal plane. 34 An inverted microscope (Nikon 90i, Japan) was used to image the bubbles with a 40× objective (NA = 0.6), and a CCD camera (DS-Fil 5Mega pixel, Nikon, Japan) was used to take 10 images for each sample. Microbubble size and concentration were analyzed using a custom MATLAB script.…”

Section: Methodsmentioning

confidence: 99%

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QCM-D Investigations on Cholesterol–DNA Tethering of Liposomes to Microbubbles for Therapy

et al. 2023

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Lipid-shelled microbubbles (MBs) offer potential as theranostic agents, capable of providing both contrast enhancement in ultrasound imaging as well as a route for triggered drug release and improved localized drug delivery. A common motif in the design of such therapeutic vehicles is the attachment of the drug carrier, often in the form of liposomes, to the microbubble. Traditionally, such attachments have been based around biotin−streptavidin and maleimide−PDP chemistries. Comparatively, the use of DNA−lipid tethers offers potential advantage. First, their specificity permits the construction of more complex architectures that might include bespoke combinations of different drugloaded liposomes and/or targeting groups, such as affimers or antibodies. Second, the use of dual-lipid tether strategies should increase the strength of the individual tethers tethering the liposomes to the bubbles. The ability of cholesterol−DNA (cDNA) tethers for conjugation of liposomes to supported lipid bilayers has previously been demonstrated. For in vivo applications, bubbles and liposomes often contain a proportion of polyethylene glycol (PEG) to promote stealth-like properties and increase lifetimes. However, the associated steric effects may hinder tethering of the drug payload. We show that while the presence of PEG reduced the tethering affinity, cDNA can still be used for the attachment of liposomes to a supported lipid bilayer (SLB) as measured via QCM-D. Importantly, we show, for the first time, that QCM-D can be used to study the tethering of microbubbles to SLBs using cDNA, signified by a decrease in the magnitude of the frequency shift compared to liposomes alone due to the reduced density of the MBs. We then replicate this tethering interaction in the bulk and observe attachment of liposomes to the shell of a central MB and hence formation of a model therapeutic microbubble.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…However, our recent work has shown that the HIFU treatment is also capable of inducing NB destruction. 34 …”

Section: Resultsmentioning

confidence: 99%

Section: Mb−bilayer Interactionsmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

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QCM-D Investigations on Cholesterol–DNA Tethering of Liposomes to Microbubbles for Therapy

et al. 2023

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Nanobubble Contrast Enhanced Ultrasound Imaging: A Review

Wegierak,

Nittayacharn,

Cooley

et al. 2024

WIREs Nanomed Nanobiotechnol

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Contrast‐enhanced ultrasound is currently used worldwide with clinical indications in cardiology and radiology, and it continues to evolve and develop through innovative technological advancements. Clinically utilized contrast agents for ultrasound consist of hydrophobic gas microbubbles stabilized with a biocompatible shell. These agents are used commonly in echocardiography, with emerging applications in cancer diagnosis and therapy. Microbubbles are a blood pool agent with diameters between 1 and 10 μm, which precludes their use in other extravascular applications. To expand the potential use of contrast‐enhanced ultrasound beyond intravascular applications, sub‐micron agents, often called nanobubbles or ultra‐fine bubbles, have recently emerged as a promising tool. Combining the principles of ultrasound imaging with the unique properties of nanobubbles (high concentration and small size), recent work has established their imaging potential. Contrast‐enhanced ultrasound imaging using these agents continues to gain traction, with new studies establishing novel imaging applications. We highlight the recent achievements in nonlinear nanobubble contrast imaging, including a discussion on nanobubble formulations and their acoustic characteristics. Ultrasound imaging with nanobubbles is still in its early stages, but it has shown great potential in preclinical research and animal studies. We highlight unexplored areas of research where the capabilities of nanobubbles may offer new advantages. As technology advances, this technique may find applications in various areas of medicine, including cancer detection and treatment, cardiovascular imaging, and drug delivery.

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Exploring the potential of contrast agents in breast cancer echography: current state and future directions

Monzeglio,

Melissa,

Rodolfi

et al. 2023

J Ultrasound

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Breast cancer stands as the most frequent malignancy and leading cause of death among women. Early and accurate detection of this pathology represents a crucial factor in enhancing both incidence and mortality rates. Ultrasound (US) examination has been extensively adopted in clinical practice due to its non-invasiveness, affordability, ease of implementation, and wide accessibility, thus representing a valuable first-line diagnostic tool for the study of the mammary gland. In this scenario, recent developments in nanomedicine are paving the way for new interpretations and applications of US diagnostics, which are becoming increasingly personalized based on the molecular phenotype of each tumor, allowing for more precise and accurate evaluations. This review highlights the current state-of-the-art of US diagnosis of breast cancer, as well as the recent advancements related to the application of US contrast agents to the field of molecular diagnostics, still under preclinical study.

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The Influence of Nanobubble Size and Stability on Ultrasound Enhanced Drug Delivery

Cited by 24 publications

References 61 publications

QCM-D Investigations on Cholesterol–DNA Tethering of Liposomes to Microbubbles for Therapy

QCM-D Investigations on Cholesterol–DNA Tethering of Liposomes to Microbubbles for Therapy

Nanobubble Contrast Enhanced Ultrasound Imaging: A Review

Exploring the potential of contrast agents in breast cancer echography: current state and future directions

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