Microbubble

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Microbubbles are bubbles smaller than one hundredth of a millimetre in diameter, but larger than one micrometre. They have widespread application in industry, medicine, [1] life science, [2] and food technology. [3] The composition of the bubble shell and filling material determine important design features such as buoyancy, crush strength, thermal conductivity, and acoustic properties.

Contents

They are used in medical diagnostics as a contrast agent for ultrasound imaging. [4] The gas-filled microbubbles, typically air or perfluorocarbon, oscillate, and vibrate if a sonic energy field is applied and may reflect ultrasound waves. This distinguishes the microbubbles from surrounding tissues. Because gas bubbles in liquid lack stability and would therefore quickly dissolve, microbubbles are typically encapsulated by shells. The shell is made from elastic, viscoelastic, or viscous material. Common shell materials are lipid, albumin, and protein. Materials having a hydrophilic outer layer to interact with the bloodstream and a hydrophobic inner layer to house the gas molecules are thermodynamically stable. Air, sulfur hexafluoride, and perfluorocarbon gases all can serve as the composition of the microbubble interior. Microbubbles with one or more incompressible liquid or solid cores surrounded by gas are referred to as microscopic or endoskeletal antibubbles. For increased stability and persistence in the bloodstream, gases with high molecular weight as well as low solubility in the blood are attractive candidates for microbubble gas cores. [5]

Microbubbles may be used for drug delivery, [6] biofilm removal, [7] membrane cleaning [8] [9] /biofilm control and water/waste water treatment purposes. [10] They are also produced by the movement of a ship’s hull through water, creating a bubble layer; this may interfere with the use of sonar because of the tendency of the layer to absorb or reflect sound waves. [11]

Acoustic response

Contrast in ultrasound imaging relies on the difference in acoustic impedance, a function of both the speed of the ultrasound wave and the density of the tissues, [12] between tissues or regions of interest. [5] As the sound waves induced by ultrasound interact with a tissue interface, some of the waves are reflected back to the transducer. The larger the difference, the more waves are reflected, and the higher the signal to noise ratio. Hence, microbubbles that have a core with a density orders of magnitude lower than and compress more readily than the surrounding tissues and blood, afford high contrast in imaging. [5]

Therapeutic application

Physical Response

When exposed to ultrasound, microbubbles oscillate in response to the incoming pressure waves in one of two ways. With lower pressures, higher frequencies, and larger microbubble diameter, microbubbles oscillate, or cavitate, stably. [5]   This causes microstreaming near the surrounding vasculature and tissues, inducing shear stresses that can create pores on the endothelial layer. [13] This pore formation enhances endocytosis and permeability. [13] At lower frequencies, higher pressures, and lower microbubble diameter, microbubbles oscillate inertially; they expand and contract violently, ultimately leading to microbubble collapse. [14] This phenomenon can create mechanical stresses and microjets along the vascular wall, which has been shown to disrupt tight cellular junctions as well as induce cellular permeability. [13] Extremely high pressures cause small vessel destruction, but the pressure can be tuned to only create transient pores in vivo. [5] [14] microbubble destruction serves as a desirable method for drug delivery vehicles. The resulting force from destruction can dislodge the therapeutic payload present on the microbubble and simultaneously sensitize the surrounding cells for drug uptake. [14]

Drug Delivery

Microbubbles can serve as drug delivery vehicles in a variety of methods. The most notable of these include: (1) incorporating a lipophilic drug to the lipid monolayer, (2) attaching nanoparticles and liposomes to the microbubble surface, (3) enveloping the microbubble within a larger liposome, and (4) electrostatically bonding nucleic acids to the microbubble surface. [5] [15] [16] [17]

I. Lipophilic Drugs

Microbubbles can facilitate the local targeting of hydrophobic drugs through the incorporation of these agents into the microbubble lipid shell. [18] [19] [20] [21] [22] [23] [24] [25] This encapsulation technique reduces systemic toxicity,  increases drug localization, and improves the solubility of hydrophobic drugs. [19] For increased localization, a targeting ligand can be appended to the exterior of the microbubble. [20] [21] [23] [24] [25] This improves treatment efficacy. [21] One drawback of the lipid-encapsulated microbubble as a drug delivery vehicle is its low payload efficacy. To combat this, an oil shell can be incorporated to the interior of the lipid monolayer to enhance payload efficacy. [26]

II. Nanoparticle and Liposome Attachment

Attachment of liposomes [27] [28] [29] [30] or nanoparticles [13] [31] [32] [33] [34] to the exterior of the lipid microbubble has also been explored to increase microbubble payload. Upon microbubble destruction with ultrasound, these smaller particles can extravasate into the tumor tissue. Furthermore, through attachment of these particles to microbubbles as opposed to co-injection, the drug is confined to the blood stream instead of accumulating in healthy tissues, and the treatment is relegated to the location of ultrasound therapy. [29] This microbubble modification is particularly attractive for Doxil, a lipid formulation of Doxorubicin already in clinical use. [29] An analysis of nanoparticle infiltration due to microbubble destruction indicates that higher pressures are necessary for vascular permeability and likely improves treatment by promoting local fluid movement and enhancing endocytosis. [13]

III. Microbubble Loading Inside Liposome

Another novel acoustically responsive microbubble system is the direct encapsulation of microbubbles inside of a liposome. Theses systems circulate longer in the body than microbubbles alone do, as this packaging method prevents the microbubble from dissolving in the blood stream. [35] Hydrophilic drugs persist in the aqueous media inside the liposome, while hydrophobic drugs congregate in the lipid bilayer. [35] [36] It has been shown in vitro that macrophages do not engulf these particles. [36]

IV. Gene Delivery through Electrostatic Interactions   

Microbubbles also serve a non-viral vector for gene transfection through electrostatic bonds between a positively charged microbubble outer shell and negatively charged nucleic acids. The transient pores formed by microbubble collapse allow the genetic material to pass into the target cells in a safer and more specific manner than current treatment methods. [37] Microbubbles have been used to deliver microRNAs, [38] [39] plasmids, [40] small interfering RNA, [41] and messenger RNA. [42] [43]

Disadvantages of Microbubbles for Drug Delivery

  • Microbubbles do not extravasate easily due to their large size, and hence their effects are relegated to the vasculature. Nanodroplets, perfluorocarbon liquid droplets surrounded by a lipid shell that vaporize due to an ultrasound pulse, offer a small diameter to promote extravasation and afford an alternative to microbubbles.
  • Microbubbles have short half-lives on the order of minutes in circulation, which limits the treatment time.
  • Microbubbles are filtered by the liver and spleen, and any drug conjugation would then also potentially pose a toxicity threat to these organs, should the microbubbles not have already released their cargo.
  • Drug conjugations to microbubbles are complicated for translation, and these formulations would be difficult to scale up for widespread use.
  • There can be a small amount hemorrhage into brain tissue when microbubbles are used to disrupt the blood brain barrier, though this is thought to be reversible.[ citation needed ]

Unique Applications of Microbubbles for Therapeutic Application

Microbubbles used for drug delivery not only serve as drug vehicles but also as a means to permeate otherwise impenetrable barriers, specifically the blood brain barrier, and to alter the tumor microenvironment.

I. Blood Brain Barrier Disruption

The brain is protected by tight junctions in the endothelial cell wall in the capillaries, known as the blood-brain barrier (BBB). [44] The BBB strictly regulates what passes into the brain from the blood, and while this function is highly desirable in healthy individuals, it also poses a barrier for therapeutics to enter the brain for cancer patients. Ultrasound was shown to disrupt the blood brain barrier in the mid 20th century, [45] and in the early 2000’s, microbubbles were shown to assist in a temporary permeabilization. [46] Since then, ultrasound and microbubble therapy has been used to deliver therapeutics to the brain. As BBB disruption with ultrasound and microbubble treatment has shown to be a safe and promising treatment pre-clinically, two clinical trials are testing delivery of doxorubicin [47] and carboplatin [48] with microbubbles to increase drug concentration locally.

II. Immunotherapy

In addition to permeating the blood brain barrier, ultrasound and microbubble therapy can alter the tumor environment and serve as an immunotherapeutic treatment. [49] High-intensity focused ultrasound (HIFU) alone triggers an immune response, speculated to be through facilitating the release of tumor antigens for immune cell recognition, activating antigen-presenting cells and promoting their infiltration, combatting tumor immunosuppression, and promoting a Th1 cell response. [50] [51] Typically, HIFU is used for thermal ablation of tumors. Low-intensity focused ultrasound (LIFU) in combination with microbubbles has also shown to stimulate immunostimulatory effects, inhibiting tumor growth and increasing endogenous leukocyte infiltration. [50] [52] Furthermore, lowering the acoustic power required for HIFU yields a safer treatment for the patient, as well as diminished treatment time. [53] Though the treatment itself shows potential, a combinatorial treatment is speculated to be required for a complete treatment. Ultrasound and microbubble treatment without additional drugs impeded the growth of small tumors but required a combinatorial drug treatment to affect medium-sized tumor growth. [54] With their immune stimulating mechanism, ultrasound and microbubbles offer a unique ability to prime or enhance immunotherapies for more effective cancer treatment.

Related Research Articles

<span class="mw-page-title-main">Liposome</span> Composite structures made of phospholipids and may contain small amounts of other molecules

A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug delivery vehicles for administration of pharmaceutical drugs and nutrients, such as lipid nanoparticles in mRNA vaccines, and DNA vaccines. Liposomes can be prepared by disrupting biological membranes.

<span class="mw-page-title-main">Anthracycline</span> Class of antibiotics

Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from Streptomyces bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, bladder cancer, and lung cancers. The first anthracycline discovered was daunorubicin, which is produced naturally by Streptomyces peucetius, a species of Actinomycetota. Clinically the most important anthracyclines are doxorubicin, daunorubicin, epirubicin and idarubicin.

<span class="mw-page-title-main">Contrast-enhanced ultrasound</span>

Contrast-enhanced ultrasound (CEUS) is the application of ultrasound contrast medium to traditional medical sonography. Ultrasound contrast agents rely on the different ways in which sound waves are reflected from interfaces between substances. This may be the surface of a small air bubble or a more complex structure. Commercially available contrast media are gas-filled microbubbles that are administered intravenously to the systemic circulation. Microbubbles have a high degree of echogenicity. There is a great difference in echogenicity between the gas in the microbubbles and the soft tissue surroundings of the body. Thus, ultrasonic imaging using microbubble contrast agents enhances the ultrasound backscatter, (reflection) of the ultrasound waves, to produce a sonogram with increased contrast due to the high echogenicity difference. Contrast-enhanced ultrasound can be used to image blood perfusion in organs, measure blood flow rate in the heart and other organs, and for other applications.

<span class="mw-page-title-main">Cationic liposome</span>

Cationic liposomes are spherical structures that contain positively charged lipids. Cationic liposomes can vary in size between 40 nm and 500 nm, and they can either have one lipid bilayer (monolamellar) or multiple lipid bilayers (multilamellar). The positive charge of the phospholipids allows cationic liposomes to form complexes with negatively charged nucleic acids through ionic interactions. Upon interacting with nucleic acids, cationic liposomes form clusters of aggregated vesicles. These interactions allow cationic liposomes to condense and encapsulate various therapeutic and diagnostic agents in their aqueous compartment or in their lipid bilayer. These cationic liposome-nucleic acid complexes are also referred to as lipoplexes. Due to the overall positive charge of cationic liposomes, they interact with negatively charged cell membranes more readily than classic liposomes. This positive charge can also create some issues in vivo, such as binding to plasma proteins in the bloodstream, which leads to opsonization. These issues can be reduced by optimizing the physical and chemical properties of cationic liposomes through their lipid composition. Cationic liposomes are increasingly being researched for use as delivery vectors in gene therapy due to their capability to efficiently transfect cells. A common application for cationic liposomes is cancer drug delivery.

<span class="mw-page-title-main">Drug delivery</span> Methods for delivering drugs to target sites

Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to drug preparation, route of administration, site-specific targeting, metabolism, and toxicity are used to optimize efficacy and safety, and to improve patient convenience and compliance. Drug delivery is aimed at altering a drug's pharmacokinetics and specificity by formulating it with different excipients, drug carriers, and medical devices. There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. Some research has also been focused on improving safety for the person administering the medication. For example, several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury.

Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. This means of delivery is largely founded on nanomedicine, which plans to employ nanoparticle-mediated drug delivery in order to combat the downfalls of conventional drug delivery. These nanoparticles would be loaded with drugs and targeted to specific parts of the body where there is solely diseased tissue, thereby avoiding interaction with healthy tissue. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. The conventional drug delivery system is the absorption of the drug across a biological membrane, whereas the targeted release system releases the drug in a dosage form. The advantages to the targeted release system is the reduction in the frequency of the dosages taken by the patient, having a more uniform effect of the drug, reduction of drug side-effects, and reduced fluctuation in circulating drug levels. The disadvantage of the system is high cost, which makes productivity more difficult, and the reduced ability to adjust the dosages.

Therapeutic ultrasound refers generally to any type of ultrasonic procedure that uses ultrasound for therapeutic benefit. Physiotherapeutic ultrasound was introduced into clinical practice in the 1950s, with lithotripsy introduced in the 1980s. Others are at various stages in transitioning from research to clinical use: HIFU, targeted ultrasound drug delivery, trans-dermal ultrasound drug delivery, ultrasound hemostasis, cancer therapy, and ultrasound assisted thrombolysis It may use focused ultrasound (FUS) or unfocused ultrasound.

<span class="mw-page-title-main">Sonoporation</span> Technique in molecular biology

Sonoporation, or cellular sonication, is the use of sound in the ultrasonic range for increasing the permeability of the cell plasma membrane. This technique is usually used in molecular biology and non-viral gene therapy in order to allow uptake of large molecules such as DNA into the cell, in a cell disruption process called transfection or transformation. Sonoporation employs the acoustic cavitation of microbubbles to enhance delivery of these large molecules. The exact mechanism of sonoporation-mediated membrane translocation remains unclear, with a few different hypotheses currently being explored.

<span class="mw-page-title-main">Arginylglycylaspartic acid</span> Chemical compound

Arginylglycylaspartic acid (RGD) is the most common peptide motif responsible for cell adhesion to the extracellular matrix (ECM), found in species ranging from Drosophila to humans. Cell adhesion proteins called integrins recognize and bind to this sequence, which is found within many matrix proteins, including fibronectin, fibrinogen, vitronectin, osteopontin, and several other adhesive extracellular matrix proteins. The discovery of RGD and elucidation of how RGD binds to integrins has led to the development of a number of drugs and diagnostics, while the peptide itself is used ubiquitously in bioengineering. Depending on the application and the integrin targeted, RGD can be chemically modified or replaced by a similar peptide which promotes cell adhesion.

Drug delivery to the brain is the process of passing therapeutically active molecules across the blood–brain barrier into the brain. This is a complex process that must take into account the complex anatomy of the brain as well as the restrictions imposed by the special junctions of the blood–brain barrier.

<span class="mw-page-title-main">Sonodynamic therapy</span>

Sonodynamic therapy (SDT) is a noninvasive treatment, often used for tumor irradiation, that utilizes a sonosensitizer and the deep penetration of ultrasound to treat lesions of varying depths by reducing target cell number and preventing future tumor growth. Many existing cancer treatment strategies cause systemic toxicity or cannot penetrate tissue deep enough to reach the entire tumor; however, emerging ultrasound stimulated therapies could offer an alternative to these treatments with their increased efficiency, greater penetration depth, and reduced side effects. Sonodynamic therapy could be used to treat cancers and other diseases, such as atherosclerosis, and diminish the risk associated with other treatment strategies since it induces cytotoxic effects only when externally stimulated by ultrasound and only at the cancerous region, as opposed to the systemic administration of chemotherapy drugs.

Nanoparticles for drug delivery to the brain is a method for transporting drug molecules across the blood–brain barrier (BBB) using nanoparticles. These drugs cross the BBB and deliver pharmaceuticals to the brain for therapeutic treatment of neurological disorders. These disorders include Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and brain tumors. Part of the difficulty in finding cures for these central nervous system (CNS) disorders is that there is yet no truly efficient delivery method for drugs to cross the BBB. Antibiotics, antineoplastic agents, and a variety of CNS-active drugs, especially neuropeptides, are a few examples of molecules that cannot pass the BBB alone. With the aid of nanoparticle delivery systems, however, studies have shown that some drugs can now cross the BBB, and even exhibit lower toxicity and decrease adverse effects throughout the body. Toxicity is an important concept for pharmacology because high toxicity levels in the body could be detrimental to the patient by affecting other organs and disrupting their function. Further, the BBB is not the only physiological barrier for drug delivery to the brain. Other biological factors influence how drugs are transported throughout the body and how they target specific locations for action. Some of these pathophysiological factors include blood flow alterations, edema and increased intracranial pressure, metabolic perturbations, and altered gene expression and protein synthesis. Though there exist many obstacles that make developing a robust delivery system difficult, nanoparticles provide a promising mechanism for drug transport to the CNS.

<span class="mw-page-title-main">Focused ultrasound for intracranial drug delivery</span> Medical technique

Focused ultrasound for intracrainial drug delivery is a non-invasive technique that uses high-frequency sound waves to disrupt tight junctions in the blood–brain barrier (BBB), allowing for increased passage of therapeutics into the brain. The BBB normally blocks nearly 98% of drugs from accessing the central nervous system, so FUS has the potential to address a major challenge in intracranial drug delivery by providing targeted and reversible BBB disruption. Using FUS to enhance drug delivery to the brain could significantly improve patient outcomes for a variety of diseases including Alzheimer's disease, Parkinson's disease, and brain cancer.

<span class="mw-page-title-main">Reduction-sensitive nanoparticles</span> Drug delivery method

Reduction-sensitive nanoparticles (RSNP) consist of nanocarriers that are chemically responsive to reduction. Drug delivery systems using RSNP can be loaded with different drugs that are designed to be released within a concentrated reducing environment, such as the tumor-targeted microenvironment. Reduction-Sensitive Nanoparticles provide an efficient method of targeted drug delivery for the improved controlled release of medication within localized areas of the body.

pH-responsive tumor-targeted drug delivery is a specialized form of targeted drug delivery that utilizes nanoparticles to deliver therapeutic drugs directly to cancerous tumor tissue while minimizing its interaction with healthy tissue. Scientists have used drug delivery as a way to modify the pharmacokinetics and targeted action of a drug by combining it with various excipients, drug carriers, and medical devices. These drug delivery systems have been created to react to the pH environment of diseased or cancerous tissues, triggering structural and chemical changes within the drug delivery system. This form of targeted drug delivery is to localize drug delivery, prolongs the drug's effect, and protect the drug from being broken down or eliminated by the body before it reaches the tumor.

Ultrasound-triggered drug delivery using stimuli-responsive hydrogels refers to the process of using ultrasound energy for inducing drug release from hydrogels that are sensitive to acoustic stimuli. This method of approach is one of many stimuli-responsive drug delivery-based systems that has gained traction in recent years due to its demonstration of localization and specificity of disease treatment. Although recent developments in this field highlight its potential in treating certain diseases such as COVID-19, there remain many major challenges that need to be addressed and overcome before more related biomedical applications are clinically translated into standard of care.

Intranasal drug delivery occurs when particles are inhaled into the nasal cavity and transported directly into the nervous system. Though pharmaceuticals can be injected into the nose, some concerns include injuries, infection, and safe disposal. Studies demonstrate improved patient compliance with inhalation. Treating brain diseases has been a challenge due to the blood brain barrier. Previous studies evaluated the efficacy of delivery therapeutics through intranasal route for brain diseases and mental health conditions. Intranasal administration is a potential route associated with high drug transfer from nose to brain and drug bioavailability.

Focused-ultrasound-mediated diagnostics or FUS-mediated diagnostics are an area of clinical diagnostic tools that use ultrasound to detect diseases and cancers. Although ultrasound has been used for imaging in various settings, focused-ultrasound refers to the detection of specific cells and biomarkers under flow combining ultrasound with lasers, microbubbles, and imaging techniques. Current diagnostic techniques for detecting tumors and diseases using biopsies often include invasive procedures and require improved accuracy, especially in cases such as glioblastoma and melanoma. The field of FUS-mediated diagnostics targeting cells and biomarkers is being investigated for overcoming these limitations.

<span class="mw-page-title-main">Ligand-targeted liposome</span> Ligand-targeted liposomes for use in medical applications

A ligand-targeted liposome (LTL) is a nanocarrier with specific ligands attached to its surface to enhance localization for targeted drug delivery. The targeting ability of LTLs enhances cellular localization and uptake of these liposomes for therapeutic or diagnostic purposes. LTLs have the potential to enhance drug delivery by decreasing peripheral systemic toxicity, increasing in vivo drug stability, enhancing cellular uptake, and increasing efficiency for chemotherapeutics and other applications. Liposomes are beneficial in therapeutic manufacturing because of low batch-to-batch variability, easy synthesis, favorable scalability, and strong biocompatibility. Ligand-targeting technology enhances liposomes by adding targeting properties for directed drug delivery.

<span class="mw-page-title-main">Artificial white blood cells</span> Alternative method of immunotherapy

Artificial white blood cells are typically membrane bound vesicles designed to mimic the immunomodulatory behavior of naturally produced leukocytes. While extensive research has been done with regards to artificial red blood cells and platelets for use in emergency blood transfusions, research into artificial white blood cells has been focused on increasing the immunogenic response within a host to treat cancer or deliver drugs in a more favorable fashion. While certain limitations have prevented leukocyte mimicking particles from becoming widely used and FDA approved, more research is being allocated to this area of synthetic blood which has the potential for producing a new form of treatment for cancer and other diseases.

References

  1. ↑ Rodríguez-Rodríguez, Javier; Sevilla, Alejandro; Martínez-Bazán, Carlos; Gordillo, José Manuel (3 January 2015). "Generation of Microbubbles with Applications to Industry and Medicine". Annual Review of Fluid Mechanics. 47 (1): 405–429. Bibcode:2015AnRFM..47..405R. doi: 10.1146/annurev-fluid-010814-014658 . ISSN   0066-4189 . Retrieved 28 March 2023.
  2. ↑ Zeng, Wenlong; Yue, Xiuli; Dai, Zhifei (19 October 2022). "Ultrasound contrast agents from microbubbles to biogenic gas vesicles". Medical Review. 3: 31–48. doi: 10.1515/mr-2022-0020 . ISSN   2749-9642. S2CID   252972129.
  3. ↑ Lu, Jiakai; Jones, Owen G.; Yan, Weixin; Corvalan, Carlos M. (27 March 2023). "Microbubbles in Food Technology". Annual Review of Food Science and Technology. 14 (1): 495–515. doi: 10.1146/annurev-food-052720-113207 . ISSN   1941-1413. PMID   36972154. S2CID   257764672.
  4. ↑ Blomley, Martin J K; Cooke, Jennifer C; Unger, Evan C; Monaghan, Mark J; Cosgrove, David O (2001). "Science, medicine, and the future: Microbubble contrast agents: A new era in ultrasound". BMJ. 322 (7296): 1222–5. doi:10.1136/bmj.322.7296.1222. PMC   1120332 . PMID   11358777.
  5. 1 2 3 4 5 6 Martin, K. Heath; Dayton, Paul A. (July 2013). "Current status and prospects for microbubbles in ultrasound theranostics: Current status and prospects for microbubbles". Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 5 (4): 329–345. doi:10.1002/wnan.1219. PMC   3822900 . PMID   23504911.
  6. ↑ Sirsi, Shashank; Borden, Mark (2009). "Microbubble compositions, properties and biomedical applications". Bubble Science, Engineering & Technology. 1 (1–2): 3–17. doi:10.1179/175889709X446507. PMC   2889676 . PMID   20574549.
  7. ↑ Mukumoto, Mio; Ohshima, Tomoko; Ozaki, Miwa; Konishi, Hirokazu; Maeda, Nobuko; Nakamura, Yoshiki (2012). "Effect of microbubbled water on the removal of a biofilm attached to orthodontic appliances — an in vitro study". Dental Materials Journal. 31 (5): 821–7. doi: 10.4012/dmj.2012-091 . PMID   23037846.
  8. ↑ Agarwal, Ashutosh; Ng, Wun Jern; Liu, Yu (January 1, 2013). "Cleaning of biologically fouled membranes with self-collapsing microbubbles". Biofouling. 29 (1): 69–76. doi:10.1080/08927014.2012.746319. PMID   23194437. S2CID   19107010 – via Taylor and Francis+NEJM.
  9. ↑ Agarwal, Ashutosh; Ng, Wun Jern; Liu, Yu, (2012). "Cleaning of biologically fouled membranes with self-collapsing microbubbles". Biofouling29 (1): 69-76. doi:10.1080/08927014.2012.746319 [ permanent dead link ]
  10. ↑ Agarwal, Ashutosh; Ng, Wun Jern; Liu, Yu (2011). "Principle and applications of microbubble and nanobubble technology for water treatment". Chemosphere. 84 (9): 1175–80. Bibcode:2011Chmsp..84.1175A. doi:10.1016/j.chemosphere.2011.05.054. PMID   21689840.
  11. ↑ Griffiths, Brian; Sabto, Michele (25 June 2012). "Quiet on board please: science underway". ECOS.
  12. ↑ Cikes, Maja; D’hooge, Jan; Solomon, Scott D. (2019), "Physical Principles of Ultrasound and Generation of Images", Essential Echocardiography, Elsevier, pp. 1–15.e1, doi:10.1016/b978-0-323-39226-6.00001-1, ISBN   978-0-323-39226-6, S2CID   67264821
  13. 1 2 3 4 5 Snipstad, Sofie; Berg, Sigrid; Mørch, Ýrr; Bjørkøy, Astrid; Sulheim, Einar; Hansen, Rune; Grimstad, Ingeborg; van Wamel, Annemieke; Maaland, Astri F.; Torp, Sverre H.; Davies, Catharina de Lange (November 2017). "Ultrasound Improves the Delivery and Therapeutic Effect of Nanoparticle-Stabilized Microbubbles in Breast Cancer Xenografts". Ultrasound in Medicine & Biology. 43 (11): 2651–2669. doi: 10.1016/j.ultrasmedbio.2017.06.029 . PMID   28781149.
  14. 1 2 3 Hernot, Sophie; Klibanov, Alexander L. (June 2008). "Microbubbles in ultrasound-triggered drug and gene delivery". Advanced Drug Delivery Reviews. 60 (10): 1153–1166. doi:10.1016/j.addr.2008.03.005. PMC   2720159 . PMID   18486268.
  15. ↑ Klibanov, Alexander L. (March 2006). "Microbubble Contrast Agents: Targeted Ultrasound Imaging and Ultrasound-Assisted Drug-Delivery Applications". Investigative Radiology. 41 (3): 354–362. doi:10.1097/01.rli.0000199292.88189.0f. ISSN   0020-9996. PMID   16481920. S2CID   27546582.
  16. ↑ Ibsen, Stuart; Schutt; Esener (May 2013). "Microbubble-mediated ultrasound therapy: a review of its potential in cancer treatment". Drug Design, Development and Therapy. 7: 375–88. doi: 10.2147/DDDT.S31564 . ISSN   1177-8881. PMC   3650568 . PMID   23667309.
  17. ↑ Mullick Chowdhury, Sayan; Lee, Taehwa; Willmann, Jürgen K. (2017-07-01). "Ultrasound-guided drug delivery in cancer". Ultrasonography. 36 (3): 171–184. doi:10.14366/usg.17021. ISSN   2288-5919. PMC   5494871 . PMID   28607323.
  18. ↑ Tinkov, Steliyan; Coester, Conrad; Serba, Susanne; Geis, Nicolas A.; Katus, Hugo A.; Winter, Gerhard; Bekeredjian, Raffi (December 2010). "New doxorubicin-loaded phospholipid microbubbles for targeted tumor therapy: In-vivo characterization". Journal of Controlled Release. 148 (3): 368–372. doi:10.1016/j.jconrel.2010.09.004. PMID   20868711.
  19. 1 2 Ren, Shu-Ting; Liao, Yi-Ran; Kang, Xiao-Ning; Li, Yi-Ping; Zhang, Hui; Ai, Hong; Sun, Qiang; Jing, Jing; Zhao, Xing-Hua; Tan, Li-Fang; Shen, Xin-Liang (June 2013). "The Antitumor Effect of a New Docetaxel-Loaded Microbubble Combined with Low-Frequency Ultrasound In Vitro: Preparation and Parameter Analysis". Pharmaceutical Research. 30 (6): 1574–1585. doi:10.1007/s11095-013-0996-5. ISSN   0724-8741. PMID   23417512. S2CID   18668573.
  20. 1 2 Liu, Hongxia; Chang, Shufang; Sun, Jiangchuan; Zhu, Shenyin; Pu, Caixiu; Zhu, Yi; Wang, Zhigang; Xu, Ronald X. (2014-01-06). "Ultrasound-Mediated Destruction of LHRHa-Targeted and Paclitaxel-Loaded Lipid Microbubbles Induces Proliferation Inhibition and Apoptosis in Ovarian Cancer Cells". Molecular Pharmaceutics. 11 (1): 40–48. doi:10.1021/mp4005244. ISSN   1543-8384. PMC   3903397 . PMID   24266423.
  21. 1 2 3 Pu, Caixiu; Chang, Shufang; Sun, Jiangchuan; Zhu, Shenyin; Liu, Hongxia; Zhu, Yi; Wang, Zhigang; Xu, Ronald X. (2014-01-06). "Ultrasound-Mediated Destruction of LHRHa-Targeted and Paclitaxel-Loaded Lipid Microbubbles for the Treatment of Intraperitoneal Ovarian Cancer Xenografts". Molecular Pharmaceutics. 11 (1): 49–58. doi:10.1021/mp400523h. ISSN   1543-8384. PMC   3899929 . PMID   24237050.
  22. ↑ Kang, Juan; Wu, Xiaoling; Wang, Zhigang; Ran, Haitao; Xu, Chuanshan; Wu, Jinfeng; Wang, Zhaoxia; Zhang, Yong (January 2010). "Antitumor Effect of Docetaxel-Loaded Lipid Microbubbles Combined With Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors". Journal of Ultrasound in Medicine. 29 (1): 61–70. doi: 10.7863/jum.2010.29.1.61 . PMID   20040776. S2CID   35510004.
  23. 1 2 Li, Yan; Huang, Wenqi; Li, Chunyan; Huang, Xiaoteng (2018). "Indocyanine green conjugated lipid microbubbles as an ultrasound-responsive drug delivery system for dual-imaging guided tumor-targeted therapy". RSC Advances. 8 (58): 33198–33207. Bibcode:2018RSCAd...833198L. doi: 10.1039/C8RA03193B . ISSN   2046-2069. PMC   9086377 . PMID   35548112.
  24. 1 2 Su, Jilian; Wang, Junmei; Luo, Jiamin; Li, Haili (August 2019). "Ultrasound-mediated destruction of vascular endothelial growth factor (VEGF) targeted and paclitaxel loaded microbubbles for inhibition of human breast cancer cell MCF-7 proliferation". Molecular and Cellular Probes. 46: 101415. doi:10.1016/j.mcp.2019.06.005. PMID   31228519. S2CID   195298987.
  25. 1 2 Li, Tiankuan; Hu, Zhongqian; Wang, Chao; Yang, Jian; Zeng, Chuhui; Fan, Rui; Guo, Jinhe (2020). "PD-L1-targeted microbubbles loaded with docetaxel produce a synergistic effect for the treatment of lung cancer under ultrasound irradiation". Biomaterials Science. 8 (5): 1418–1430. doi: 10.1039/C9BM01575B . ISSN   2047-4830. PMID   31942578.
  26. ↑ Unger, Evan C.; McCREERY, Thomas P.; Sweitzer, Robert H.; Caldwell, Veronica E.; Wu, Yunqiu (December 1998). "Acoustically Active Lipospheres Containing Paclitaxel: A New Therapeutic Ultrasound Contrast Agent". Investigative Radiology. 33 (12): 886–892. doi:10.1097/00004424-199812000-00007. ISSN   0020-9996. PMID   9851823.
  27. ↑ Escoffre, J.; Mannaris, C.; Geers, B.; Novell, A.; Lentacker, I.; Averkiou, M.; Bouakaz, A. (January 2013). "Doxorubicin liposome-loaded microbubbles for contrast imaging and ultrasound-triggered drug delivery". IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. 60 (1): 78–87. doi:10.1109/TUFFC.2013.2539. ISSN   0885-3010. PMID   23287915. S2CID   5540324.
  28. ↑ Deng, Zhiting; Yan, Fei; Jin, Qiaofeng; Li, Fei; Wu, Junru; Liu, Xin; Zheng, Hairong (January 2014). "Reversal of multidrug resistance phenotype in human breast cancer cells using doxorubicin-liposome–microbubble complexes assisted by ultrasound". Journal of Controlled Release. 174: 109–116. doi:10.1016/j.jconrel.2013.11.018. PMID   24287101.
  29. 1 2 3 Lentacker, Ine; Geers, Bart; Demeester, Joseph; De Smedt, Stefaan C; Sanders, Niek N (January 2010). "Design and Evaluation of Doxorubicin-containing Microbubbles for Ultrasound-triggered Doxorubicin Delivery: Cytotoxicity and Mechanisms Involved". Molecular Therapy. 18 (1): 101–108. doi:10.1038/mt.2009.160. PMC   2839231 . PMID   19623162.
  30. ↑ Lentacker, Ine; Geers, Bart; Demeester, Jo; De Smedt, Stefaan C.; Sanders, Niek N. (November 2010). "Tumor cell killing efficiency of doxorubicin loaded microbubbles after ultrasound exposure". Journal of Controlled Release. 148 (1): e113–e114. doi:10.1016/j.jconrel.2010.07.085. PMID   21529584.
  31. ↑ Gong, Yuping; Wang, Zhigang; Dong, Guifang; Sun, Yang; Wang, Xi; Rong, Yue; Li, Maoping; Wang, Dong; Ran, Haitao (2014-11-04). "Low-intensity focused ultrasound mediated localized drug delivery for liver tumors in rabbits". Drug Delivery. 23 (7): 2280–2289. doi: 10.3109/10717544.2014.972528 . ISSN   1071-7544. PMID   25367869. S2CID   41067520.
  32. ↑ Lee; Moon; Han; Lee; Kim; Lee; Ha; Kim; Chung (2019-04-24). "Antitumor Effects of Intra-Arterial Delivery of Albumin-Doxorubicin Nanoparticle Conjugated Microbubbles Combined with Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors". Cancers. 11 (4): 581. doi: 10.3390/cancers11040581 . ISSN   2072-6694. PMC   6521081 . PMID   31022951.
  33. ↑ Ha, Shin-Woo; Hwang, Kihwan; Jin, Jun; Cho, Ae-Sin; Kim, Tae Yoon; Hwang, Sung Il; Lee, Hak Jong; Kim, Chae-Yong (2019-05-24). "Ultrasound-sensitizing nanoparticle complex for overcoming the blood-brain barrier: an effective drug delivery system". International Journal of Nanomedicine. 14: 3743–3752. doi: 10.2147/ijn.s193258 . PMC   6539164 . PMID   31213800.
  34. ↑ Liufu, Chun; Li, Yue; Tu, Jiawei; Zhang, Hui; Yu, Jinsui; Wang, Yi; Huang, Pintong; Chen, Zhiyi (2019-11-15). "Echogenic PEGylated PEI-Loaded Microbubble As Efficient Gene Delivery System". International Journal of Nanomedicine. 14: 8923–8941. doi: 10.2147/ijn.s217338 . PMC   6863126 . PMID   31814720.
  35. 1 2 Wrenn, Steven; Dicker, Stephen; Small, Eleanor; Mleczko, Michal (September 2009). "Controlling cavitation for controlled release". 2009 IEEE International Ultrasonics Symposium. Rome: IEEE. pp. 104–107. doi:10.1109/ULTSYM.2009.5442045. ISBN   978-1-4244-4389-5. S2CID   34883820.
  36. 1 2 Ibsen, Stuart; Benchimol, Michael; Simberg, Dmitri; Schutt, Carolyn; Steiner, Jason; Esener, Sadik (November 2011). "A novel nested liposome drug delivery vehicle capable of ultrasound triggered release of its payload". Journal of Controlled Release. 155 (3): 358–366. doi:10.1016/j.jconrel.2011.06.032. PMC   3196035 . PMID   21745505.
  37. ↑ Rychak, Joshua J.; Klibanov, Alexander L. (June 2014). "Nucleic acid delivery with microbubbles and ultrasound". Advanced Drug Delivery Reviews. 72: 82–93. doi:10.1016/j.addr.2014.01.009. PMC   4204336 . PMID   24486388.
  38. ↑ Meng, Lingwu; Yuan, Shaofei; Zhu, Linjia; ShangGuan, Zongxiao; Zhao, Renguo (2019-09-13). "Ultrasound-microbubbles-mediated microRNA-449a inhibits lung cancer cell growth via the regulation of Notch1". OncoTargets and Therapy. 12: 7437–7450. doi: 10.2147/ott.s217021 . PMC   6752164 . PMID   31686849.
  39. ↑ Wang, Xiaowei; Searle, Amy; Hohmann, Jan David; Liu, Leo; Abraham, Meike; Palasubramaniam, Jathushan; Lim, Bock; Yao, Yu; Wallert, Maria; Yu, Eefang; Chen, Yung; Peter, Karlheinz (July 2017). "Dual-Targeted Theranostic Delivery of miRs Arrests Abdominal Aortic Aneurysm Development". Molecular Therapy. 26 (4): 1056–1065. doi:10.1016/j.ymthe.2018.02.010. PMC   6080135 . PMID   29525742.
  40. ↑ Cai, Junhong; Huang, Sizhe; Yi, Yuping; Bao, Shan (May 2019). "Ultrasound microbubble-mediated CRISPR/Cas9 knockout of C-erbB-2 in HEC-1A cells". Journal of International Medical Research. 47 (5): 2199–2206. doi:10.1177/0300060519840890. ISSN   0300-0605. PMC   6567764 . PMID   30983484.
  41. ↑ Zhao, Ranran; Liang, Xiaolong; Zhao, Bo; Chen, Min; Liu, Renfa; Sun, Sujuan; Yue, Xiuli; Wang, Shumin (August 2018). "Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer". Biomaterials. 173: 58–70. doi:10.1016/j.biomaterials.2018.04.054. PMID   29758547. S2CID   206080519.
  42. ↑ Abraham, Meike; Peter, Karlheinz; Michel, Tatjana; Wendel, Hans; Krajewski, Stefanie; Wang, Xiaowei (April 2017). "Nanoliposomes for safe and efficient therapeutic mRNA delivery: A step toward nanotheranostics in inflammatory and cardiovascular diseases as well as cancer". Nanotheranostics. 1 (2): 154–165. doi:10.7150/ntno.19449. PMC   5646717 . PMID   29071184.
  43. ↑ Michel, Tatjana; Luft, Daniel; Abraham, Meike; Reinhardt, Sabina; Medinal, Martha; Kurz, Julia; Schaller, Martin; Avci-Adali, Meltem; Schlensak, Christian; Peter, Karlheinz; Wendel, Hans; Wang, Xiaowei; Krajewski, Stefanie (July 2017). "Cationic Nanoliposomes Meet mRNA: Efficient Delivery of Modified mRNA Using Hemocompatible and Stable Vectors for Therapeutic Applications". Molecular Therapy Nucleic Acids. 8: 459–468. doi:10.1016/j.omtn.2017.07.013. PMC   5545769 . PMID   28918045.
  44. ↑ Abbott, N. Joan; Patabendige, Adjanie A.K.; Dolman, Diana E.M.; Yusof, Siti R.; Begley, David J. (January 2010). "Structure and function of the blood–brain barrier". Neurobiology of Disease. 37 (1): 13–25. doi:10.1016/j.nbd.2009.07.030. PMID   19664713. S2CID   14753395.
  45. ↑ Bakay, L. (1956-11-01). "Ultrasonically Produced Changes in the Blood-Brain Barrier". Archives of Neurology and Psychiatry. 76 (5): 457–67. doi:10.1001/archneurpsyc.1956.02330290001001. ISSN   0096-6754. PMID   13371961.
  46. ↑ Hynynen, Kullervo; McDannold, Nathan; Vykhodtseva, Natalia; Jolesz, Ferenc A. (September 2001). "Noninvasive MR Imaging–guided Focal Opening of the Blood-Brain Barrier in Rabbits". Radiology. 220 (3): 640–646. doi:10.1148/radiol.2202001804. ISSN   0033-8419. PMID   11526261.
  47. ↑ "A Study to Evaluate the Safety and Feasibility of Blood-Brain Barrier Disruption Using Transcranial MRI-Guided Focused Ultrasound With Intravenous Ultrasound Contrast Agents in the Treatment of Brain Tumours With Doxorubicin". January 23, 2020 – via clinicaltrials.gov.
  48. ↑ "A Study to Evaluate the Safety of Transient Opening of the Blood-Brain Barrier by Low Intensity Pulsed Ultrasound With the SonoCloud Implantable Device in Patients With Recurrent Glioblastoma Before Chemotherapy Administration". October 10, 2018 – via clinicaltrials.gov.
  49. ↑ Escoffre, Jean-Michel; Deckers, Roel; Bos, Clemens; Moonen, Chrit (2016), Escoffre, Jean-Michel; Bouakaz, Ayache (eds.), "Bubble-Assisted Ultrasound: Application in Immunotherapy and Vaccination", Therapeutic Ultrasound, Springer International Publishing, vol. 880, pp. 243–261, doi:10.1007/978-3-319-22536-4_14, ISBN   978-3-319-22535-7, PMID   26486342
  50. 1 2 Liu, Hao-Li; Hsieh, Han-Yi; Lu, Li-An; Kang, Chiao-Wen; Wu, Ming-Fang; Lin, Chun-Yen (2012). "Low-pressure pulsed focused ultrasound with microbubbles promotes an anticancer immunological response". Journal of Translational Medicine. 10 (1): 221. doi: 10.1186/1479-5876-10-221 . ISSN   1479-5876. PMC   3543346 . PMID   23140567.
  51. ↑ Shi, Guilian; Zhong, Mingchuan; Ye, Fuli; Zhang, Xiaoming (November 2019). "Low-frequency HIFU induced cancer immunotherapy: tempting challenges and potential opportunities". Cancer Biology & Medicine. 16 (4): 714–728. doi:10.20892/j.issn.2095-3941.2019.0232. ISSN   2095-3941. PMC   6936245 . PMID   31908890.
  52. ↑ Sta Maria, Naomi S.; Barnes, Samuel R.; Weist, Michael R.; Colcher, David; Raubitschek, Andrew A.; Jacobs, Russell E. (2015-11-10). Mondelli, Mario U. (ed.). "Low Dose Focused Ultrasound Induces Enhanced Tumor Accumulation of Natural Killer Cells". PLOS ONE. 10 (11): e0142767. Bibcode:2015PLoSO..1042767S. doi: 10.1371/journal.pone.0142767 . ISSN   1932-6203. PMC   4640510 . PMID   26556731.
  53. ↑ Suzuki, Ryo; Oda, Yusuke; Omata, Daiki; Nishiie, Norihito; Koshima, Risa; Shiono, Yasuyuki; Sawaguchi, Yoshikazu; Unga, Johan; Naoi, Tomoyuki; Negishi, Yoichi; Kawakami, Shigeru (March 2016). "Tumor growth suppression by the combination of nanobubbles and ultrasound". Cancer Science. 107 (3): 217–223. doi:10.1111/cas.12867. PMC   4814255 . PMID   26707839.
  54. ↑ Lin, Win-Li; Lin, Chung-Yin; Tseng, Hsiao-Ching; Shiu, Heng-Ruei; Wu, Ming-Fang (April 2012). "Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug". International Journal of Nanomedicine. 7: 2143–52. doi: 10.2147/IJN.S29514 . ISSN   1178-2013. PMC   3356217 . PMID   22619550.
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