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OBJECTIVE: The objective of this study was to develop and optimize palbociclib-loaded nanobubbles for targeted breast cancer therapy. MATERIALS AND METHODS: Biocompatible poly(DL-lactide-co-glycolide) was used to create nanobubbles loaded with palbociclib. The formulation process was meticulously crafted using a three-level Box-Behnken design and a double emulsion solvent evaporation method to precisely tailor the nanobubbles' properties. RESULTS: The Derringer's desirability method optimized variables by transforming responses into a desirability scale, resulting in a global desirability value. Optimal settings, A: 526.97 mg, B: 250 mg, C: 2.0% w/v, D: 6101 rpm, achieved a D value of 0.949. Palbociclib nanobubbles demonstrated a smaller particle size (31.78 ± 2.12) than plain nanobubbles (38.56 ± 3.56). PDI values indicated a uniform size distribution. The zeta potential remained consistent, with values of -31.34 ± 3.36 for plain and -31.56 ± 3.12 for drug-loaded nanobubbles. Encapsulation efficiency was 70.12%, highlighting effective drug encapsulation. Palbociclib release was significantly higher from nanobubbles in pH 7.4, especially with ultrasound, releasing almost 99.34% of the drug. Hemolytic activity assays confirmed safety for injection. Fluorescent intensity analysis revealed a two-fold increase in cellular uptake of palbociclib facilitated by ultrasound. The MTT assay demonstrated enhanced cytotoxicity of palbociclib-loaded nanobubbles, especially with ultrasound, emphasizing their potential for improved therapeutic efficacy. The IC50 values for palbociclib, without ultrasound, and with ultrasound were 98.3 µM, 72.34 µM, and 61.34 µM, respectively. CONCLUSION: The significant findings of this study emphasize the potential of palbociclib-loaded nanobubbles as a promising therapeutic system for improved breast cancer treatment.

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Nanobubbles are sub- micron-sized gas entities that find applications in a wide  range of scientific fields. Typically, they are thought to  diffuse according to Brownian motion. We report the  existence of self-propelled motion of oxygen bulk  nanobubbles in ultrapure water at body temperature.  Their motion, to a large extent, is self-affine; there are  different scaling exponents along the x- and y-axes as  well as for the lateral displacement. We use fractal  analysis, and we calculate the structure function, the  normalised velocity autocorrelation function, the  skewness, and the kurtosis. All descriptors attest the  existence of a quasi-Gaussian stochastic process, which  is classified as fractional Brownian motion. More than 50 \% of the trajectories along the x-axis follow  superdiffusion, while this amount drops to 30 \% for  motion along the y-axis as a result of the asymmetry of  the field of view.

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Understanding characteristics of graphite-water interface is of scientific significance and practical importance. Ordered stripe structures have been observed at this interface, with their origins debated between condensed gas molecules and airborne hydrocarbons. Atomic force microscopy (AFM) studies have revealed variations in the morphology, formation and growth of these ordered structures. Here, we investigate the graphite-water interface under different environmental conditions using PeakForce Quantitative Nanomechanical (PF-QNM) AFM. Our findings reveal that stripe structures with 4 nm width and 0.5 nm periodicity, form and grow under wet laboratory conditions but not in pure inert gas or cleanroom environments. These stripes appear more readily when the graphite surface is immersed in water, with growth associated with gas nanodomains on the surface. This suggests that atmospheric contaminants migrate to the water-graphite interface, potentially facilitated by gas states.  These findings underscore the impact of environmental conditions on graphitic materials, providing new insights into the mechanisms underlying stripe formation and growth.

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Micro and nanobubbles (MNBs), as an efficient and convenient method, have been widely used in water treatment. Composed of gas and water, MNBs avoid directly introducing potential secondary pollutants. Notably, MNBs exhibit significant advantages through interface reactions in assisting AOPs. They overcome barriers like low mass transfer coefficients and limited reactive sites, and shorten the distance between pollutants and oxidants, achieving higher pollutant removal efficiency. However, there is a lack of systematic summary and in-depth discussion on the fundamental mechanisms of MNBs-assisted AOPs. In this critical review, the characteristics of MNBs related to water treatment are outlined first. Subsequently, the recent applications, performance, and mechanisms of MNBs-assisted AOPs including ozone, plasma, photocatalytic, and Fenton oxidation are overviewed. We conclude that MNBs can improve pollutant removal mainly by enhancing the utilization of reactive oxygen species (ROS) generated by AOPs due to the effective interface reactions. Furthermore, we calculated the electrical energy per order of reaction (EE/O) parameter of different MNBs-assisted AOPs, suggesting that MNBs can reduce the total energy consumption in most of the tested cases. Finally, future research needs/opportunities are proposed. The fundamental insights in this review are anticipated to further facilitate an in-depth understanding of the mechanisms of MNBs-assisted AOPs and supply critical guidance on developing MNBs-based technologies for water treatment.

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Surface-attached micro- and nanobubbles are known for their resistance to external forces. This study experimentally and theoretically investigates their response to strong ultrasonic fields. Surface-attached micro- and nanobubbles with contact radii from 2 µm to 20 µm are generated in a microchannel and exposed to ultrasound through a vibrating glass substrate. At a driving frequency over 200 kHz up to 2 MHz tested, no significant response from the micro- and nanobubbles is observed. By contrast, at 100 kHz-200 kHz, ultrasonic cavitation bubbles appear in the microchannel and migrate toward the surface micro- and nanobubbles. Then the surface micro- and nanobubbles merge with the ultrasonic cavitation bubbles, detach from the substrate, and become free gaseous nuclei susceptible to further cavitation. Notably, the removal process leaves no observable residue. Theoretical analysis suggests that the directional migration of cavitation bubbles is driven by mutual acoustic radiation forces. This work demonstrates that ultrasonic fields can effectively remove surface micro- and nanobubbles, transforming them into free gaseous cavitation nuclei.

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The piezoelectric properties of two-dimensional semiconductor nanobubbles present remarkable potential for application in flexible optoelectronic devices, and the piezoelectric field has emerged as an efficacious pathway for both the separation and migration of photogenerated electron-hole pairs, along with inhibition of recombination. However, the comprehension and control of photogenerated carrier dynamics within nanobubbles still remain inadequate. Hence, this study is dedicated to underscore the importance of in situ detection and detailed characterization of photogenerated electron-hole pairs in nanobubbles to enrich understanding and strategic manipulation in two-dimensional semiconductor materials. Utilizing frequency modulation kelvin probe force microscopy (FM-KPFM) and strain gradient distribution techniques, the existence of a piezoelectric field in monolayer WS2 nanobubbles was confirmed. Combining w/o and with illumination FM-KPFM, second-order capacitance gradient technique and in situ nanoscale tip-enhanced photoluminescence characterization techniques, the interrelationships among the piezoelectric effect, interlayer carrier transfer, and the funneling effect for photocarrier dynamics process across various nanobubble sizes were revealed. Notably, for a WS2/graphene bubble height of 15.45 nm, a 0 mV surface potential difference was recorded in the bubble region w/o and with illumination, indicating a mutual offset of piezoelectric effect, interlayer carrier transfer, and the funneling effect. This phenomenon is prevalent in transition metal dichalcogenides materials exhibiting inversion symmetry breaking. The implication of our study is profound for advancing the understanding of the dynamics of photogenerated electron-hole pair in nonuniform strain piezoelectric systems, and offers a reliable framework for the separation and modulation of photogenerated electron-hole pair in flexible optoelectronic devices and photocatalytic applications.

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Cancer development is related to genetic mutations in primary cells, where 5-10% of all cancers are derived from acquired genetic defects, most of which are a consequence of the environment and lifestyle. As it turns out, over half of cancer deaths are due to the generation of drug resistance. The local delivery of chemotherapeutic drugs may reduce their toxicity by increasing their therapeutic dose at targeted sites and by decreasing the plasma levels of circulating drugs. Nanobubbles have attracted much attention as an effective drug distribution system due to their non-invasiveness and targetability. This review aims to present the characteristics of nanobubble systems and their efficacy within the biomedical field with special emphasis on cancer treatment. In vivo and in vitro studies on cancer confirm nanobubbles' ability and good blood capillary perfusion; however, there is a need to define their safety and side effects in clinical trials.

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Exogenous enzyme-activated prodrug therapy (EPT) is a potential cancer treatment strategy that delivers non-human enzymes into or on the surface of the cell and subsequently converts a non-toxic prodrug into an active cytotoxic substance at a specific location and time. The development of several pharmacological pairs based on EPT has been the focus of anticancer research for more than three decades. Numerous of these pharmacological pairs have progressed to clinical trials, and a few have achieved application in specific cancer therapies. The current review highlights the potential of enzyme-activated prodrug therapy as a promising anticancer treatment. Different microbial, plant, or viral enzymes and their corresponding prodrugs that advanced to clinical trials have been listed. Additionally, we discuss new trends in the field of enzyme-activated prodrug nanocarriers, including nanobubbles combined with ultrasound (NB/US), mesoscopic-sized polyion complex vesicles (PICsomes), nanoparticles, and extracellular vesicles (EVs), with special emphasis on smart stimuli-triggered drug release, hybrid nanocarriers, and the main application of nanotechnology in improving prodrugs.

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Purpose: Osteosarcoma (OS) is the most common type of primary malignant bone tumor. Transducing a functional TP53 gene can effectively inhibit OS cell activity. Poly lactic acid-glycolic acid (PLGA) nanobubbles (NBs) mediated by focused ultrasound (US) can introduce exogenous genes into target cells in animal models, but this technique relies on the passive free diffusion of agents across the body. The inclusion of superparamagnetic iron oxide (SPIO) in microbubbles allows for magnetic-based tissue localization. A low-intensity-focused ultrasound (LIFU) instrument was developed at our institute, and different intensities of LIFU can either disrupt the NBs (RLI-LIFU) or exert cytocidal effects on the target tissues (RHI-LIFU). Based on these data, we performed US-magnetic-mediated TP53-NB destruction and investigated its ability to inhibit OS growth when combined with LIFU both in vitro and in vivo. Methods: Several SPIO/TP53/PLGA (STP) NB variants were prepared and characterized. For the in vitro experiments, HOS and MG63 cells were randomly assigned into five treatment groups. Cell proliferation and the expression of TP53 were detected by CCK8, qRT-PCR and Western blotting, respectively. In vivo, tumor-bearing nude mice were randomly assigned into seven treatment groups. The iron distribution of Perls' Prussian blue-stained tissue sections was determined by optical microscopy. TUNEL-DAPI was performed to examine apoptosis. TP53 expression was detected by qRT-PCR and immunohistochemistry. Results: SPIO/TP53/PLGA NBs with a particle size of approximately 200 nm were prepared successfully. For in vitro experiments, ultrasound-targeted transfection of TP53 overexpression in OS cells and efficient inhibition of OS proliferation have been demonstrated. Furthermore, in a tumor-bearing nude mouse model, RLI-LIFU-magnetic-mediated SPIO/TP53/PLGA NBs increased the transfection efficiency of the TP53 plasmid, resulting in apoptosis. Adding RHI-LIFU to the treatment regimen significantly increased the apoptosis of OS cells in vivo. Conclusion: Combining LIFU and US-magnetic-mediated SPIO/TP53/PLGA NB destruction is potentially a novel noninvasive and targeted therapy for OS.

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The removal of oil from solid surfaces, such as textiles and plates, remains a challenge due to the strong binding affinity of the oil. Conventional methods for surface cleaning often require surfactants and mechanical abrasion to enhance the cleaning process. However, in excess, these can pose adverse effects on the environment and to the material. This study investigated how bulk nanobubble water can clean oil microdroplets deposited on surfaces like glass coverslips and dishes. Microscopy imaging and further image analysis clearly revealed that these microdroplets detached from both hydrophobic and hydrophilic surfaces when washed with bulk nanobubble water within a fluidic microchannel. Oil contaminant cleaning was also conducted in water as mobile phase to mimic the circumstances that occur in a dishwasher and washing machine. Cleaning on a larger scale also proved very successful in the removal of oil from a porcelain bowl. These results indicate that nanobubble water can easily remove oil contaminants from glass and porcelain surfaces without the assistance of surfactants. This is in stark contrast to negligible results obtained with a control solution without nanobubbles. This study indicates that nanobubble technology is an innovative, low-cost, eco-friendly approach for oil removal, demonstrating its potential for broad practical applications.

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Integrated aquaculture wastewater treatment systems (IAWTSs) are widely used in treating aquaculture wastewater with the aeration-microalgae unit serving as an important component. In this study, we artificially constructed an IAWTS and applied two aeration-microalgae methods: ordinary aeration or ozone nanobubbles (ONBs) with microalgae (Nannochloropsis oculata). The impact of N.oculata and ONBs on the removal performance of nutrients and the underlying micro-ecological mechanisms were investigated using 16S rRNA gene amplicon sequencing. The results demonstrated that the combined use of ONBs and N.oculata exhibited superior purification effects with 78.25%, 76.59% and 86.71% removal of CODMn, TN and TP. N.oculata played a pivotal role as the primary element in wastewater purification, while ONBs influenced nutrient dynamics by affecting both N.oculata and bacterial communities. N.oculata actively shaped bacterial communities, with a specific focus on nitrogen and phosphorus cycling in the micro-environment remodeled by ONBs. Rare bacterial communities displayed heightened activity in response to the changes in N.oculata, ONBs, and nutrient levels. These findings provide a novel approach to improve the technological processes the IAWTS, contributing to the advancement of sustainable aquaculture practices by offering valuable insights into wastewater purification efficiency and micro-ecological mechanisms.

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Thyroxine (T4) is a drug extensively utilized for the treatment of hypothyroidism. However, the oral absorption of T4 presents certain limitations. This research investigates the efficacy of CO2 nanobubbles in water as a potential oral carrier for T4 administration to C57BL/6 hypothyroid mice. Following 18 h of fasting, the formulation was administered to the mice, demonstrating that the combination of CO2 nanobubbles and T4 enhanced the drug's absorption in blood serum by approximately 40%. To comprehend this observation at a molecular level, we explored the interaction mechanism through which T4 engages with the CO2 nanobubbles, employing molecular simulations, semi-empirical quantum mechanics, and PMF calculations. Our simulations revealed a high affinity of T4 for the water-gas interface, driven by additive interactions between the hydrophobic region of T4 and the gas phase and electrostatic interactions of the polar groups of T4 with water at the water-gas interface. Concurrently, we observed that at the water-gas interface, the cluster of T4 formed in the water region disassembles, contributing to the drug's bioavailability. Furthermore, we examined how the gas within the nanobubbles aids in facilitating the drug's translocation through cell membranes. This research contributes to a deeper understanding of the role of CO2 nanobubbles in drug absorption and subsequent release into the bloodstream. The findings suggest that utilizing CO2 nanobubbles could enhance T4 bioavailability and cell permeability, leading to more efficient transport into cells. Additional research opens the possibility of employing lower concentrations of this class of drugs, thereby potentially reducing the associated side effects due to poor absorption.

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The advent of air nanobubbles (ANBs) has opened up a wide range of commercial applications spanning industries including wastewater treatment, food processing, biomedical engineering, and agriculture. The implementation of electric field-based air nanobubbles (EF-ANBs) irrigation presents a promising approach to enhance agricultural crop efficiency, concurrently promoting environmentally sustainable practices through reducing fertilizer usage. This study investigated the impact of EF-ANBs on the germination and overall growth of agricultural crops in soil. Results indicate a substantial enhancement in both germination rates and plant growth upon the application of EF-ANBs. Notably, the introduction of ANBs led to a significant enhancement in the germination rate of lettuce and basil, increasing from approximately 20% to 96% and from 16% to 53%, respectively over two days. Moreover, the presence of EF-ANBs facilitates superior hypocotyl elongation, exhibiting a 2.8- and a 1.6-fold increase in the elongation of lettuce and basil, respectively, over a six-day observation period. The enriched oxygen levels within the air nanobubbles expedite aerobic respiration, amplifying electron leakage from the electron transport chain (ETC) and resulting in heightened reactive oxygen species (ROS) production, playing a pivotal role in stimulating growth signaling. Furthermore, the application of EF-ANBs in irrigation surpasses the impact of traditional fertilizers, demonstrating a robust catalytic effect on the shoot, stem, and root length, as well as the leaf count of lettuce plants. Considering these parameters, a single fertilizer treatment (at various concentrations) during EF-ANBs administration, demonstrates superior plant growth compared to regular water combined with fertilizer. The findings underscore the synergistic interaction between aerobic respiration and the generation of ROS in promoting plant growth, particularly in the context of reduced fertilizer levels facilitated by the presence of EF-ANBs. This promising correlation holds significant potential in establishing more sustainability for ever-increasing environmentally conscious agriculture.

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In recent years, enveloped micro-nanobubbles have garnered significant attention in research due to their commendable stability, biocompatibility, and other notable properties. Currently, the preparation methods of enveloped micro-nanobubbles have limitations such as complicated preparation process, large bubble size, wide distribution range, low yield, etc. There exists an urgent demand to devise a simple and efficient method for the preparation of enveloped micro-nanobubbles, ensuring both high concentration and a uniform particle size distribution. Magnetic lipid bubbles (MLBs) are a multifunctional type of enveloped micro-nanobubble combining magnetic nanoparticles with lipid-coated bubbles. In this study, MLBs are prepared simply and efficiently by a magneto internal heat bubble generation process based on the interfacial self-assembly of iron oxide nanoparticles induced by the thermogenic effect in an alternating magnetic field. The mean hydrodynamic diameter of the MLBs obtained was 384.9 ± 8.5 nm, with a polydispersity index (PDI) of 0.248 ± 0.021, a zeta potential of -30.5 ± 1.0 mV, and a concentration of (7.92 ± 0.46) × 109 bubbles/mL. Electron microscopy results show that the MLBs have a regular spherical stable core-shell structure. The superparamagnetic iron oxide nanoparticles (SPIONs) and phospholipid layers adsorbed around the spherical gas nuclei of the MLBs, leading the particles to demonstrate commendable superparamagnetic and magnetic properties. In addition, the effects of process parameters on the morphology of MLBs, including phospholipid concentration, phospholipid proportiona, current intensity, magnetothermal time, and SPION concentration, were investigated and discussed to achieve controlled preparation of MLBs. In vitro imaging results reveal that the higher the concentration of MLBs loaded with iron oxide nanoparticles, the better the in vitro ultrasound (US) imaging and magnetic resonance imaging (MRI) results. This study proves that the magneto internal heat bubble generation process is a simple and efficient technique for preparing MLBs with high concentration, regular structure, and commendable properties. These findings lay a robust foundation for the mass production and application of enveloped micro-nanobubbles, particularly in biomedical fields and other related domains.

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Determining the role of micro-nanobubbles (MNBs) in controlling the risk posed by pathogens to soil and groundwater during reclaimed water irrigation requires clarification of the mechanism of how MNBs block pathogenic bacteria. In this study, real-time bioluminescence imaging was used to investigate the effects of MNBs on the transport and spatiotemporal distribution of bioluminescent Escherichia coli 652T7 strain in porous media. The presence of MNBs significantly increased the retention of bacteria in the porous media, decreasing the maximum relative effluent concentration (C/C0) by 78 % from 0.97 (without MNBs) to 0.21 (with MNBs). The results suggested that MNBs provided additional sites at the air-water interface (AWI) for bacterial attachment and acted as physical obstacles to reduce bacterial passage. These effects varied with environmental conditions such as solution ionic strength and pore water velocity. The results indicated that MNBs enhanced electrostatic attachment of bacteria at the AWI and their mechanical straining in pores. This study suggests that adding MNBs in pathogen-containing water is an effective measure for increasing filtration efficiency and reducing the risk of pathogenic contamination during agricultural irrigation.

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Cl- activated peroxymonosulfate (PMS) oxidation technology can effectively degrade pollutants, but the generation of chlorinated disinfection byproducts (DBPs) limits the application of this technology in water treatment. In this study, a method of nanobubbles (NBs) synergistic Cl-/PMS system was designed to try to improve this technology. The results showed the synergistic effects of NBs/Cl-/PMS were significant and universal while its upgrade rate was from 12.89% to 34.97%. Moreover, the synergistic effects can be further improved by increasing the concentration and Zeta potential of NBs. The main synergistic effects of NBs/Cl-/PMS system were due to the electrostatic attraction of negatively charged NBs to Na+ from NaCl, K+ from PMS, and H+ from phenol, which acted as a "bridge" between Cl- and HSO5- as well as phenol and Cl-/HSO5-, increasing active substance concentration. In addition, the addition of NBs completely changed the oxidation system of Cl-/PMS from one that increases environmental toxicity to one that reduces it. The reason was that the electrostatic attraction of NBs changed the active sites and degradation pathway of phenol, greatly reducing the production of highly toxic DBPs. This study developed a novel environmentally friendly oxidation technology, which provides an effective strategy to reduce the generation of DBPs in the Cl-/PMS system.

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This study investigated the performance of combined nanobubble water (NW) and digestate in the soaking hydrolysis process. Two types of NW (CO2NW and O2NW) with digestate were used to soak rice straw for 1, 2, 3, 5, and 7 days. During soaking process, the volatile fatty acids (VFA) concentration in the treatment with O2NW and digestate for 3 days (O2NW-3 d) reached 7179.5 mg-HAc/L. Moreover, the highest specific methane yield (SMY) obtained in this treatment could reach 336.7 NmL/gVS. Although the addition of NW did not significantly increase SMY from digestate soaking, NW could accelerate the rate of methane production and reduce digestion time of T80. The enrichment of Enterobacter in the soaking process was observed when using CO2NW and O2NW as soaking solutions which played important roles in VFA production. This study provides a new insight into environment-friendly enhanced crop straw pretreatment, combining NW and digestate soaking hydrolysis.

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Introduction: Recently, nanobubbles (NBs) have gained significant traction in the field of tumor diagnosis and treatment owing to their distinctive advantages. However, the application of NBs is limited due to their restricted size and singular reflection section, resulting in low ultrasonic reflection. Methods: We synthesized a nano-scale ultrasound contrast agent (IR783-SiO2NPs@NB) by encapsulating SiO2 nanoparticles in an IR783-labeled lipid shell using an improved film hydration method. We characterized its physicochemical properties, examined its microscopic morphology, evaluated its stability and cytotoxicity, and assessed its contrast-enhanced ultrasound imaging capability both in vitro and in vivo. Results: The results show that IR783-SiO2NPs@NB had a "donut-type" composite microstructure, exhibited uniform particle size distribution (637.2 ± 86.4 nm), demonstrated excellent stability (30 min), high biocompatibility, remarkable tumor specific binding efficiency (99.78%), and an exceptional contrast-enhanced ultrasound imaging capability. Conclusion: Our newly developed multiple scattering NBs with tumor targeting capacity have excellent contrast-enhanced imaging capability, and they show relatively long contrast enhancement duration in solid tumors, thus providing a new approach to the structural design of NBs.

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Nanobubbles (NBs) are classified in two distinct categories: surface and bulk. Surface NBs are readily observed using atomic force microscopy (AFM), while the existence of bulk NBs has been a subject of debate, conflicting with the diffusion theory's predictions. Current methodologies for identifying bulk NBs yield inconclusive results. In this study, Langmuir Blodgett (LB) technique and AFM, are utilized to visualize NB imprints on anionic, cationic and zwitterionic lipid films deposited on glass-slide substrates. Our analysis of Langmuir monolayers compression isotherms reveals the impact of bulk NBs on lipid monolayer development. AFM scans of the deposited lipid films consistently show NB imprints. Notably, cationic and zwitterionic film depositions exhibit NB formations from the 1st layer, whereas in anionic films, these formations are observed only after the 3rd layer. These results suggest that the origin of these imprinted formations may be attributed to bulk NBs.

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KEY POLICY HIGHLIGHTSNanobubbles and nanoparticles may enhance the polyphenols' bioavailabilityNanobubbles may stimulate the activation of Nrf2 and detox enzymesArmoured oxygen nanobubbles may enhance radiotherapy or chemotherapy effects.

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