Surface Of Microbubbles Research Articles

Ultrasound Molecular Imaging Enhances High-Intensity Focused Ultrasound Ablation on Liver Cancer With B7-H3-Targeted Microbubbles.

High-intensity focused ultrasound (HIFU) is a promising minimally invasive treatment for liver cancer; however, its efficacy is often limited by the attenuation of ultrasonic energy. This study investigates the effectiveness of B7-H3-targeted microbubbles (T-MBs) in enhancing HIFU ablation of liver cancer and explores their potential for clinical translation. T-MBs and isotype control microbubbles (I-MBs) were synthesized through the conjugation of biotinylated anti-B7-H3 antibody and isotype control antibody to the microbubble surface, respectively. Contrast-enhanced ultrasound imaging was performed to compare the accumulation of T-MBs and I-MBs in liver cancer at various time points. The efficacy of T-MBs in enhancing HIFU treatment was evaluated by measuring the immediate tumor ablation rate and long-term tumor growth suppression. Additionally, the induced antitumor immune response was assessed through cytokine quantification in serum and tumor tissue, along with immunofluorescence staining conducted on days 1, 3, and 7 post-treatment. T-MBs demonstrated superior liver cancer-specific accumulation, characterized by higher concentrations and prolonged retention compared to I-MBs. The combination of T-MBs with HIFU resulted in significantly enhanced tumor ablation rates and superior tumor growth suppression. Post-treatment analysis revealed a gradual uptick in cytokine levels within the tumor microenvironment, along with progressive infiltration of antitumor immune cells. T-MBs effectively enhance the therapeutic efficacy of HIFU for liver cancer treatment while simultaneously promoting an antitumor immune response. These findings provide a strong experimental foundation for the clinical translation of ultrasound molecular imaging combined with HIFU as a novel approach for tumor therapy.

Spatial-temporal-controlled NO gas and PARP1 siRNA delivery for alleviating the dilemma of deeper sonodynamic therapy in pancreatic cancer

Sonodynamic therapy (SDT) for pancreatic cancer is always limited to poor drug delivery and resistance. The insufficient drug delivery is mostly associated with the abundant fibrotic stroma which consisting of a natural physical barrier. In addition, the activated DNA repair pathway associated with reactive oxygen species (ROS) therapy greatly resist and weaken the SDT efficacy. Based on these facts, we herein presented an ultrasound responsive microbubble system of PARP1 siRNA-Pyropheophorbide/SNO (P-PPaS MBs), which were self-assembled by lipids covalently conjugated with pyropheophorbide (PPa), DSPE-PEG2000-SNO, and DC-Chol, while the PARP1 siRNA was absorbed onto the surface of microbubbles. Upon local ultrasound irradiation, the in situ micro-nano conversion induced cavitation effect and spatial–temporal controlled release of NO mediated by ROS generated from pyropheophorbide could facilitate the deeper penetration of sonosensitizer and siRNA at pancreatic tumor sites. SDT could effectively kill tumor cells, while PARP1 inhibition blocked the DNA repair pathway to further enhance the tumor killing efficiency. Therefore, controlled NO self-supply and gene therapy assisted SDT had the potential to be an effective strategy for deeper pancreatic cancer therapy.

Dynamics and frequency response analysis of encapsulated microbubble under nonlinear ultrasound

Bubble dynamic behavior and frequency response of encapsulated microbubbles in nonlinear acoustic field is significant in applications such as tumor therapy, thrombolysis, tissue destruction, and ultrasonic lithotripsy. The acoustic cavitation effect includes stable cavitation and transient cavitation. The transformation from stable cavitation to transient cavitation requires a certain threshold, which is also called the transient cavitation threshold. Phospholipid-coated microbubbles are commonly used to enhance acoustic cavitation. However, the acoustic effects of different coating materials are not very clear, especially when considering the nonlinear effects caused by diffraction, scattering, and reflection during ultrasonic propagation. In this paper, the bubble dynamic behaviors and frequency responses of microbubbles under different frequencies, acoustic pressures, and viscoelastic properties of different shell materials are analyzed by coupling the Gilmore-Akulichev-Zener model with the nonlinear model of a lipid envelope and using the KZK equation to simulate the nonlinear acoustic field. At the same time, the influence of the coated material and nonlinear acoustic effects are considered. The bubble dynamic behavior and frequency response under the actually measured sound field are compared with those simulated by the KZK equation. The results show that the nonlinearity will lead the velocity of the microbubble wall to decrease, and when the pressure of ultrasound increases, the main frequency component of the microbubble oscillation increases, making the radial motion of the microbubble more violent. When the frequency changes, the closer the oscillation frequency of the microbubble is to the resonant frequency, the stronger the radial motion of the microbubble is. The coating material can change the harmonic component in the oscillation frequency. When the harmonic is close to the resonance frequency, the radial motion of the microbubble is enhanced. The elasticity of the coated material has almost no effect on the microbubble's frequency response, and the initial viscosity and surface tension of encapsulated microbubble will change the oscillation frequency distribution of encapsulated microbubble. When the initial viscosity of the coated microbubble is smaller, the subharmonic component of the microbubble oscillation increases. When the frequency of the subharmonic is closer to the resonance frequency than the main frequency, the acoustic cavitation effect is significantly enhanced. On the other hand, when the initial surface tension of the encapsulated microbubble increases, the main frequency and subharmonic component of the microbubble oscillation are enhanced, so that the acoustic cavitation effect is also enhanced. Therefore, this study can further elucidate the bubble dynamics of encapsulated microbubbles, stimulated by nonlinear ultrasound, benefiting the frequency response analysis of coated microbubbles under nonlinear acoustic fields.

Ultrasound-Stimulated "Exocytosis" by Cell-Like Microbubbles Enhances Antibacterial Species Penetration and Immune Activation Against Implant Infection.

Host immune systems serving as crucial defense lines are vital resisting mechanisms against biofilm-associated implant infections. Nevertheless, biofilms hinder the penetration of anti-bacterial species, inhibit phagocytosis of immune cells, and frustrate host inflammatory responses, ultimately resulting in the weakness of the host immune system for biofilm elimination. Herein, a cell-like construct is developed through encapsulation of erythrocyte membrane fragments on the surface of Fe3 O4 nanoparticle-fabricated microbubbles and then loaded with hydroxyurea (EMB-Hu). Under ultrasound (US) stimulation, EMB-Hu undergoes a stable oscillation manner to act in an "exocytosis" mechanism for disrupting biofilm, releasing agents, and enhancing penetration of catalytically generated anti-bacterial species within biofilms. Additionally, the US-stimulated "exocytosis" by EMB-Hu can activate pro-inflammatory macrophage polarization and enhance macrophage phagocytosis for clearance of disrupted biofilms. Collectively, this work has exhibited cell-like microbubbles with US-stimulated "exocytosis" mechanisms to overcome the biofilm barrier and signal macrophages for inflammatory activation, finally achieving favorable therapeutic effects against implant infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms.

Remote Loading: The Missing Piece for Achieving High Drug Payload and Rapid Release in Polymeric Microbubbles.

The use of drug-loaded microbubbles for targeted drug delivery, particularly in cancer treatment, has been extensively studied in recent years. However, the loading capacity of microbubbles has been limited due to their surface area. Typically, drug molecules are loaded on or within the shell, or drug-loaded nanoparticles are coated on the surfaces of microbubbles. To address this significant limitation, we have introduced a novel approach. For the first time, we employed a transmembrane ammonium sulfate and pH gradient to load doxorubicin in a crystallized form in the core of polymeric microcapsules. Subsequently, we created remotely loaded microbubbles (RLMBs) through the sublimation of the liquid core of the microcapsules. Remotely loaded microcapsules exhibited an 18-fold increase in drug payload compared with physically loaded microcapsules. Furthermore, we investigated the drug release of RLMBs when exposed to an ultrasound field. After 120 s, an impressive 82.4 ± 5.5% of the loaded doxorubicin was released, demonstrating the remarkable capability of remotely loaded microbubbles for on-demand drug release. This study is the first to report such microbubbles that enable rapid drug release from the core. This innovative technique holds great promise in enhancing drug loading capacity and advancing targeted drug delivery.

Thermal/ultrasound-triggered release of liposomes loaded with Ganoderma applanatum polysaccharide from microbubbles for enhanced tumour ablation

The effectiveness of thermal ablation for the treatment of liver tumours is limited by the risk of incomplete ablation, which can result in residual tumours. Herein, an enhancement strategy is proposed based on the controlled release of Ganoderma applanatum polysaccharide (GAP) liposome–microbubble complexes (GLMCs) via ultrasound (US)-targeted microbubble destruction (UTMD) and sublethal hyperthermic (SH) field. GLMCs were prepared by conjugating GAP liposomes onto the surface of microbubbles via biotin–avidin linkage. In vitro, UTMD promotes the cellular uptake of liposomes and leads to apoptosis of M2-like macrophages. Secretion of arginase-1 (Arg-1) and transforming growth factor-beta (TGF-β) by M2-like macrophages decreased. In vivo, restriction of tumour volume was observed in rabbit VX2 liver tumours after treatment with GLMCs via UTMD in GLMCs + SH + US group. The expression levels of CD68 and CD163, as markers of tumour-associated macrophages (TAMs) in the GLMCs + SH + US group were reduced in liver tumour tissue. Decreased Arg-1, TGF-β, Ki67, and CD31 factors related to tumour cell proliferation and angiogenesis was evident on histological analysis. In conclusion, thermal/US-triggered drug release from GLMCs suppressed rabbit VX2 liver tumour growth in the SH field by inhibiting TAMs, which represents a potential approach to improve the effectiveness of thermal ablation.

Quantitative estimation of phospholipid molecules desorbed from a microbubble surface under ultrasound irradiation

Microbubbles have potential applications as drug and gene carriers, and drug release can be triggered by externally applied ultrasound irradiation while inside blood vessels. Desorption of molecules forming the microbubble shell can be observed under ultrasound irradiation of a single isolated microbubble, and the volume of desorbed molecules can be quantitatively estimated from the contact angle between the bubble and a glass plate. Microbubbles composed of a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) shell and a poorly-soluble gas are created. When the microbubbles are exposed to a pulsed ultrasound, the contact angles increase dramatically; the percentage of DMPC molecules desorbed from the bubble surface reaches 70%. Vibration of a single bubble in the radial direction is measured using a laser Doppler vibrometer. The relationship between the vibrational characteristics and the amount of molecular desorption reveals that a larger vibrational amplitude of the bubble around the resonance size induces a larger amount of molecular desorption. These results support the possibility of controlling molecular desorption with pulsed ultrasound.

Microbiome recognition of virulence-factor-governed interfacial mechanisms in antibiotic resistance and pathogenicity removal by functionalized microbubbles

The frequent occurrence of epidemics around the world gives rise to increasing concerns of the pollution of pathogens and antibiotic resistant bacteria in water. This study investigated the impacts of virulence factors (VFs) on the removal of antibiotic resistant and pathogenic bacteria from municipal wastewater by ozone-free or ozone-encapsulated Fe(III)-coagulant-modified colloidal microbubbles (O3_free-CCMBs or O3-CCMBs). The highly interface-dependent process was initiated with cell-capture on the microbubble surface where the as-collected cells could be further inactivated with the bubble-released ozone and oxidative species if O3-CCMBs were used. The microbiome sequencing analyses denote that the O3_free-CCMB performance of antibiotic resistant and pathogenic bacteria removal was dependent on the virulence phenotypes related to cell-surface properties or structures. The adhesion-related VFs facilitated the effective attachment between cells and the coagulant-modified bubble-surface, which further enhanced cell inactivation by bubble-released ozone. On the contrary, the motility-related VFs might help cells to escape from the bubble capture by locomotion; however, this could be overcome by O3-CCMB-induced oxidative demolition of the movement structures. Besides, the microbubble performance was also impacted with the cell-membrane structure related to antibiotic resistance (i.e., efflux pumps) and the dissolved organic matter through promoting the surface-capture and decreasing the oxidation efficacy. The ozone-encapsulated microbubbles with surface functionalization are robust and promising tools in hampering antibiotic resistance and pathogenicity dissemination from wastewater to surface water environment; and awareness should be raised for the influence of virulence signatures on its performance.

Emission peak shifted incoherent random laser through the combined effects of coupling of surface plasmons in a triangular shaped silver nanostructure, microbubbles, and the waveguiding mechanism

The random laser (RL) is now becoming an essential tool for various photonics applications, and a plethora of research advancements in RL coupled with developments in the field of techniques of syntheses of various nanostructured materials is taking place. But the realization of tuning the peak emission wavelength of RL is still very challenging. However, in this report we have demonstrated an emission peak shifted tunable low threshold incoherent RL in the visible region in a gain medium of a commercially available dye laser material and by employing the rarely used scatterer materials of triangular silver nanoparticles (TSN), microbubbles, and the waveguiding mechanism. The scattering properties of trapped microbubbles, along with the localized surface plasmon resonance property of TSN of appropriate concentration within waveguided thin films composed of glass substrates, have been methodically investigated to demonstrate the reduction in lasing threshold and tunability in the peak emission wavelength. A two-fold reduction in RL threshold by addition of TSN in the disordered system, along with a considerable narrowing down of the emission spectra to a few nanometers, are obtained. Furthermore, the peak emission wavelength shift of 6 nm is reported by suitably changing the system configuration by the addition of an optimum concentration of TSN along with trapped microbubbles. The as-developed system shows high-quality laser performance with the maximum value of η=0.64, a quantity describing the ratio of the number of stimulated radiative photons within RL and the total number of emissive photons. We propose that the total internal reflections from the microbubble surface, along with plasmonic enhancement and scattering from the TSN, mediate the waveguided RL to achieve the low threshold. Therefore, this report is an early step towards demonstrating efficient RL in a ternary scattering system. Many more avenues for investigating this developing research issue may be helpful for the future development of affordable and robust optoelectronic devices.

Contrast-enhanced ultrasound combined targeted microbubbles for diagnosis of highly aggressive papillary thyroid carcinoma.

Accurate diagnosis of highly aggressive papillary thyroid cancer (PTC) may greatly help avoid overdiagnosis and overtreatment of PTC. However, there is still a lack of a convenient and accurate method. Targeted microbubbles, an emerging ultrasound contrast agent, have the potential to accurately diagnose highly aggressive PTC. To design and prepare a targeted microbubble for specific contrast-enhanced ultrasound (CEUS) imaging of highly invasive PTC. Using β-galactoside-binding protein galectin-3 (Gal-3) overexpressed on the surface of highly invasive PTC cells as a target, C12 polypeptide (ANTPCGPYTHDCPVKR) with high affinity and specificity for Gal-3 was coupled to the surface of lipid microbubbles to prepare targeted microbubbles (Gal-3-C12@lipo MBs). The targeted microbubbles were prepared by thin-film hydration method and mechanical shaking method. The morphology, diameter, concentration and stability of microbubbles were investigated by fluorescence microscopy and an AccuSizer. The biosafety of microbubbles was studied using BCPAP cells through CCK8 assay. Confocal laser scanning microscope and flow cytometry were applied to research the cellular uptake of microbubbles to investigate the targeting ability to highly aggressive PTC. Finally, the specific contrast-enhanced ultrasound imaging of microbubbles in highly invasive PTC was validated on the mice bearing subcutaneous BCPAP tumor model via a clinically ultrasound imaging system. Gal-3-C12@lipo MBs were successfully prepared which showed a well-defined spherical morphology with an average diameter of 1.598 ± 0.848 μm. Gal-3-C12@lipo MBs showed good stability without rupture within 4 hours after preparation. At the cellular level, Gal-3-C12@lipo MBs exhibited favorable biosafety and superior targeting ability to BCPAP cells, with 2.8-fold higher cellular uptake than non-targeted lipid microbubbles (Lipo MBs). At the animal level, Gal-3-C12@lipo MBs significantly improved the quality of contrast-enhanced ultrasound imaging in highly invasive PTC, with an echo intensity of tumor significantly higher than that of Lipo MBs. We designed and fabricated a novel targeted microbubble for the specific ultrasound imaging diagnosis of highly aggressive PTC. The targeted microbubbles have good stability, superior biosafety and high targeting specificity, which can significantly improve the tumor signal-to-noise ratio of highly invasive PTC, and have the potential to facilitate and accurately diagnose highly invasive PTC.

Low-intensity triggered release with spatial and temporal control using antibubbles

One approach to ultrasound therapy is to use therapeutic agents that can be activated by focused ultrasound when they reach a specific site in the body. Commonly, such agents are loaded on the surfaces of microbubbles, which respond strongly to ultrasound and shed the payload. However, microbubbles require high pressures and mechanical indices to burst (typically above 200 kPa, MI > 0.2). Moreover, the quantity and types of therapeutic payload that can be delivered by microbubbles are limited because payloads must be attached to the microbubble surface. Here, we show how these limitations can be overcome by using stabilized antibubbles as an ultrasound-responsive carrier. Antibubbles are liquid droplets encased within an air bubble. Because therapeutic payloads can be encapsulated in the core, larger volumes can be carried per antibubble. Additionally, by carrying payloads in the volume rather than on the surface, a wider variety of payloads can be carried. Through experiments we demonstrate that antibubbles respond strongly to ultrasound and can release payloads with pressures below 50 kPa (MI = 0.05) for certain formulations. By modifying the formulation, we show that the release pressure and temporal release profile can be tuned. Finally, we show that the bursting is highly selective in space, demonstrating that antibubbles can be used for precise delivery of payloads using shaped, low-intensity ultrasound fields.

PVA-Microbubbles as a Radioembolization Platform: Formulation and the In Vitro Proof of Concept.

This proof-of-concept study lays the foundations for the development of a delivery strategy for radioactive lanthanides, such as Yttrium-90, against recurrent glioblastoma. Our appealing hypothesis is that by taking advantage of the combination of biocompatible polyvinyl alcohol (PVA) microbubbles (MBs) and endovascular radiopharmaceutical infusion, a minimally invasive selective radioembolization can be achieved, which can lead to personalized treatments limiting off-target toxicities for the normal brain. The results show the successful formulation strategy that turns the ultrasound contrast PVA-shelled microbubbles into a microdevice, exhibiting good loading efficiency of Yttrium cargo by complexation with a bifunctional chelator. The selective targeting of Yttrium-loaded MBs on the glioblastoma-associated tumor endothelial cells can be unlocked by the biorecognition between the overexpressed αVβ3 integrin and the ligand Cyclo(Arg-Gly-Asp-D-Phe-Lys) at the PVA microbubble surface. Hence, we show the suitability of PVA MBs as selective Y-microdevices for in situ injection via the smallest (i.e., 1.2F) neurointerventional microcatheter available on the market and the accumulation of PVA MBs on the HUVEC cell line model of integrin overexpression, thereby providing ~6 × 10-15 moles of Y90 per HUVEC cell. We further discuss the potential impact of using such versatile PVA MBs as a new therapeutic chance for treating glioblastoma multiforme recurrence.

Dual-modal molecular imaging and therapeutic evaluation of coronary microvascular dysfunction using indocyanine green-doped targeted microbubbles.

Coronary microvascular dysfunction (CMD), which causes a series of cardiovascular diseases, seriously endangers human health. However, precision diagnosis of CMD is still challenging due to the lack of sensitive probes and complementary imaging technologies. Herein, we demonstrate indocyanine green-doped targeted microbubbles (named T-MBs-ICG) as dual-modal probes for highly sensitive near-infrared (NIR) fluorescence imaging and high-resolution ultrasound imaging of CMD in mouse models. In vitro results show that T-MBs-ICG can specifically target fibrin, a specific CMD biomarker, via the cysteine-arginine-glutamate-lysine-alanine (CREKA) peptide modified on the surface of microbubbles. We further employ T-MBs-ICG to achieve NIR fluorescence imaging of injured myocardial tissue in a CMD mouse model, leading to a signal-to-background ratio (SBR) of up to 50, which is 20 fold higher than that of the non-targeted group. Furthermore, ultrasound molecular imaging of T-MBs-ICG is obtained within 60 s after intravenous injection, providing molecular information on ventricular and myocardial structures and fibrin with a resolution of 1.033 mm × 0.466 mm. More importantly, we utilize comprehensive dual-modal imaging of T-MBs-ICG to evaluate the therapeutic efficacy of rosuvastatin, a cardiovascular drug for the clinical treatment of CMD. Overall, the developed T-MBs-ICG probes with good biocompatibility exhibit great potential in the clinical diagnosis of CMD.

Dual-Modality Molecular Imaging of Tumor via Quantum Dots-Liposome-Microbubble Complexes.

Molecular imaging has demonstrated promise for evaluating the expression levels of biomarkers for the early prediction of tumor progression and metastasis. However, most of the commonly used molecular imaging modalities are relatively single and have difficulties imaging complex biological processes. Here, we fabricated αvβ3-integrin-targeted quantum-dots-loaded liposome-microbubble (iRGD-QDLM) complexes that combined ultrasound imaging with optical imaging. The resulting iRGD-QDLM has excellent binding capability to 4T1 breast cancer cells. Ultrasound molecular imaging of 4T1 tumors demonstrated that significantly enhanced ultrasound molecular signals could be observed in comparison with non-targeted QDLM. Importantly, our study also suggested that iRGD-QDL on the surface of microbubbles could be delivered into a tumor by ultrasound-mediated microbubble destruction and adhered to αvβ3 integrin on breast cancer cells, achieving transvascular fluorescent imaging. Our study provides a novel approach to dual-modality molecular imaging of αvβ3 integrin in the tumor tissue.

Generating Lifetime-Enhanced Microbubbles by Decorating Shells with Silicon Quantum Nano-Dots Using a 3-Series T-Junction Microfluidic Device

Long-term stability of microbubbles is crucial to their effectiveness. Using a new microfluidic device connecting three T-junction channels of 100 μm in series, stable monodisperse SiQD-loaded bovine serum albumin (BSA) protein microbubbles down to 22.8 ± 1.4 μm in diameter were generated. Fluorescence microscopy confirmed the integration of SiQD on the microbubble surface, which retained the same morphology as those without SiQD. The microbubble diameter and stability in air were manipulated through appropriate selection of T-junction numbers, capillary diameter, liquid flow rate, and BSA and SiQD concentrations. A predictive computational model was developed from the experimental data, and the number of T-junctions was incorporated into this model as one of the variables. It was illustrated that the diameter of the monodisperse microbubbles generated can be tailored by combining up to three T-junctions in series, while the operating parameters were kept constant. Computational modeling of microbubble diameter and stability agreed with experimental data. The lifetime of microbubbles increased with increasing T-junction number and higher concentrations of BSA and SiQD. The present research sheds light on a potential new route employing SiQD and triple T-junctions to form stable, monodisperse, multi-layered, and well-characterized protein and quantum dot-loaded protein microbubbles with enhanced stability for the first time.

Degradation of ciprofloxacin in aqueous solution using ozone microbubbles: spectroscopic, kinetics, and antibacterial analysis

Ciprofloxacin (CIP) has been listed in the last version of the surface water due to its ability to kill human cells by inhibiting the activity of DNA topoisomerase IV. Thus, CIP, along with other antibiotic pollution has become a serious threat to the environment and public health. Ozonation has been used as an advanced technique that is applied in wastewater treatment to remove CIP, but the primary limitation of this method is the low solubility of ozone in water. This study is the first report of CIP removal in a scale-up of its aqueous solution using a self-developed aerator pump-enhanced ozonation (APO) system, which only employs a propeller and a zigzag arrangement of meshes. This aerator pump decreased the size of ozone bubbles by 90% and increased the effective ozone solubility to 0.47 ppm. The mechanism of degradation of CIP is attributed to an oxidation reaction of the antibiotic with reactive oxygen species, such as hydroxyl, oxygen, and hydroperoxyl radicals, generated on the surface of the ozone microbubbles. It was found that the rate and efficiency of degradation of CIP using the APO system were 3.64 × 10−3/min and 83.5%, respectively, which is higher compared with those of conventional flow ozonation (FO) systems (1.47 × 10−3/min and 60.9%). The higher degradation efficiency of CIP by the APO system was also revealed by its higher electrical energy efficiency (0.146 g/kWh), compared to that of the FO system (0.106 g/kWh). The degradation of CIP was also monitored by the resulting antibacterial activity against Escherichia coli and Staphylococcus aureus.

Aptamer-Functionalized Microbubbles Targeted to P-selectin for Ultrasound Molecular Imaging of Murine Bowel Inflammation.

Our objectives were to develop a targeted microbubble with an anti-P-selectin aptamer and assess its ability to detect bowel inflammation in two murine models of acute colitis. Lipid-shelled microbubbles were prepared using mechanical agitation. A rapid copper-free click chemistry approach (azide-DBCO) was used to conjugate the fluorescent anti-P-selectin aptamer (Fluor-P-Ap) to the microbubble surface. Bowel inflammation was chemically induced using 2,4,6-trinitrobenzenesulfonic acid (TNBS) in both Balb/C and interleukin-10-deficient (IL-10 KO) mice. Mouse bowels were imaged using non-linear contrast mode following an i.v. bolus of 1 × 108 microbubbles. Each mouse received a bolus of aptamer-functionalized and non-targeted microbubbles. Mouse phenotypes and the presence of P-selectin were validated using histology and immunostaining, respectively. Microbubble labelling of Fluor-P-Ap was complete after 20min at 37 ̊C. We estimate approximately 300,000 Fluor-P-Ap per microbubble and confirmed fluorescence using confocal microscopy. There was a significant increase in ultrasound molecular imaging signal from both Balb/C (p = 0.003) and IL-10 KO (p = 0.02) mice with inflamed bowels using aptamer-functionalized microbubbles in comparison to non-targeted microbubbles. There was no signal in healthy mice (p = 0.4051) using either microbubble. We constructed an aptamer-functionalized microbubble specific for P-selectin using a clinically relevant azide-DBCO click reaction, which could detect bowel inflammation in vivo. Aptamers have potential as a next generation targeting agent for developing cost-efficient and clinically translatable targeted microbubbles.

Ultrasound-triggered drug delivery for glioma therapy through gambogic acid-loaded nanobubble-microbubble complexes.

Glioma is one of the most common primary brain tumors. Gambogic acid (GA) is widely used in tumor chemotherapy. However, GA has poor water solubility, low bioavailability, and difficult permeability across the blood-brain barrier (BBB), leading to poor efficacy against brain tumors. In our study, we developed negatively charged GA-loaded PLGA nanobubbles [GA/poly(lactic-co-glycolic acid) (PLGA)] and conjugated them onto the surface of cationic lipid microbubbles (CMBs) through electrostatic interactions. The resulting GA/PLGA-CMB complex was characterized for its particle size, distribution, drug encapsulation efficiency, and ultrasound imaging property, revealing a high drug encapsulation efficiency and excellent contrast imaging capability. Importantly, significantly enhanced GA delivery into the brain could be observed after the intravenous administration of GA/PLGA-CMBs combined with low-intensity focused ultrasound (FUS) due to the cavitation from CMBs, which mediated blood-brain barrier (BBB) opening. Taking advantage of the opened BBB, GA/PLGA nanobubbles could be delivered into the tumor. Then, the second FUS irradiation at higher energy was used to induce the cavitation of GA/PLGA nanobubbles, producing the second cavitation on tumor cells, significantly enhancing the ability of GA to enter tumor cells and inhibit tumor growth inhibition efficacy.

Microbubbles for Effective Cleaning of Metal Surfaces Without Chemical Agents.

Traditional cleaning methods involving surfactants and ultrasound generate large amounts of wastewater. Microbubbles offer a more eco-friendly technology for interface cleaning. Here, we explored the efficiency of microbubbles for cleaning oil from metal surfaces. Air microbubbles at concentrations as high as 106 particles/mL were generated by hydrodynamic cavitation. Under optimal conditions, cleaning efficiencies for the removal of oil from carbon-steel and stainless-steel surfaces were 78.5 and 49.8% after 15 min, respectively, compared to only 6.5 and 9.9% without microbubbles. Additionally, combining microbubble treatment with the ultrasonic method achieved a higher efficiency than ultrasonic cleaning alone, achieving an efficiency of 85.5% after 3 min compared to 69.0%. The mechanism of microbubble cleaning was determined using a fluorescence observation system, and a model was established to describe the cleaning process. The use of microbubbles produced less emulsified oil wastewater because the oil that attaches to the microbubble surface floats with the bubbles to the surface of the cleaning water, where it can be removed, allowing for water recycling. This novel microbubble cleaning technology, which both enhances cleaning efficiency and reduces wastewater production, represents a viable and eco-friendly option for degreasing processes.

Light-induced thermal convection for collection and removal of carbon nanotubes

Carbon nanotubes (CNTs) have exhibited immense potential for applications in biology and medicine, and once their intended purpose is fulfilled, the elimination of residual CNTs is essential to avoid negative effects. In this study, we demonstrated the effective collection and simple removal of CNTs dispersed in a suspension via thermal convection. First, a tapered fiber tip with a cone angle and end diameter of 10° and 3 μm, respectively, was fabricated via a heating and pulling method. Further, a laser beam with a power and wavelength of 100 mW and 1.55 μm, respectively, was launched into the tapered fiber tip, which was placed in a CNT suspension, resulting in the formation of a microbubble on the fiber tip. The temperature gradient on the microbubble and suspension surface induced thermal convection in the suspension, which resulted in the accumulation of CNTs on the fiber tip. The experimentally formed CNT cluster possessed a circular top surface with a diameter of 87 μm and an arched cross-section with a height of 19 μm. Furthermore, this CNT cluster was firmly attached to the fiber tip. Therefore, the removal of CNT clusters can be realized by simply removing the fiber tip from the suspension. Moreover, we simulated the thermal convection that caused CNT aggregation. The obtained results indicate that convection near the fiber tip flows toward it, which pushes the CNTs toward the fiber tip and enables their attachment to it. Further, the flow velocity is symmetrically distributed as a Gaussian function, which results in the formation of a circular top surface and arched cross-sectional profile for the CNT cluster. Our method may be applied in biomedicine for the collection and removal of nano-drug residues.