Search Results (42)

Hypoxia is one of the most important factors limiting the effectiveness of modern anticancer therapies, particularly photodynamic therapy (PDT). The hypoxia of the tumor microenvironment results from abnormal angiogenesis and the high metabolic demand of cancer cells, which leads to reduced oxygen availability necessary for generating reactive oxygen species (ROS). Consequently, conventional therapeutic approaches, mainly based on the type II PDT mechanism, show limited effectiveness under hypoxic conditions. In response to these limitations, strategies are being developed to increase oxygen availability within the tumor. Of particular importance are nanocarriers based on perfluorocarbons (PFCs), which, due to their high gas solubility, can effectively transport and release oxygen in the tumor microenvironment. Research indicates that the use of such systems leads to improved PDT efficiency by increasing the production of singlet oxygen and enhancing cancer cell damage. Parallelly, alternative approaches independent of high oxygen concentration, including type I photosensitizers, are being developed. Unlike classical type II mechanisms, they generate free radicals through electron transfer reactions, which allows effective action even under conditions of significant hypoxia. This approach significantly expands the possibilities of using PDT in the treatment of tumors with low oxygen levels. Current research directions focus on integrating various therapeutic strategies to achieve a synergistic effect. Hybrid systems combining oxygen delivery (e.g., using PFCs) with the use of type I photosensitizers and other treatment methods, such as chemotherapy or immunotherapy, show the greatest clinical potential. Such multifunctional approaches simultaneously allow improving tumor oxygenation and increasing the efficiency of ROS generation, which makes them a promising strategy for the future of anticancer therapies. Full article

Background: Solid organ transplantation (SOT) is a life-saving treatment for patients with end-stage diseases and/or organ failure. However, access to healthy organs is often limited by challenges in organ preservation. Furthermore, upon transplantation, ischemia–reperfusion injury (IRI) can lead to increased organ rejection or graft failures. The work presented aims to address both challenges using an innovative nanomedicine platform for simultaneous drug and oxygen delivery. In recent studies, resveratrol (RSV), a natural antioxidant, anti-inflammatory, and reactive oxygen species (ROS) scavenging agent, has been reported to protect against IRI by inhibiting ferroptosis. Here, we report the design, development, and scalable manufacturing of the first-in-class dual-function perfluorocarbon-nanoemulsion (PFC-NE) perfusate for simultaneous oxygen and antioxidant delivery, equipped with a near-infrared fluorescence (NIRF) reporter, longitudinal, non-invasive NIRF imaging of perfusate flow through organs/tissues during machine perfusion. Methods: A Quality-by-Design (QbD)-guided optimization was used to formulate a triphasic PFC-NE with 30% w/v perfluorooctyl bromide (PFOB). Drug-free perfluorocarbon nanoemulsions (DF-NEs) and RSV-loaded nanoemulsions (RSV-NEs) were produced at 250–1000 mL scales using M110S, LM20, and M110P microfluidizers. Colloidal attributes, fluorescence stability, drug loading, and RSV release were evaluated using DLS, NIRF imaging, and HPLC, respectively. PFC-NE oxygen loading and release kinetics were evaluated during perfusion through the BMI OrganBank^® machine with the MEDOS HILITE^® oxygenator and by controlled flow of oxygen. The in vitro antioxidant activity of RSV-NE was measured using the oxygen radical scavenging antioxidant capacity (ORAC) assay. The cytotoxicity and ferroptosis inhibition of RSV-NE were evaluated in RAW 264.7 macrophages. Results: PFC-NE batches maintained a consistent droplet size (90–110 nm) and low polydispersity index (<0.3) across all scales, with high reproducibility and >80% PFOB loading. Both DF-NE and RSV-NE maintained colloidal and fluorescence stability under centrifugation, serum exposure at body temperature, filtration, 3-month storage, and oxygenation. Furthermore, RSV-NE showed high drug loading and sustained release (63.37 ± 2.48% at day 5) compared with the rapid release observed in free RSV solution. In perfusion studies, the oxygenation capacity of PFC-NE consistently exceeded that of University of Wisconsin (UW) solution and demonstrated stable, linear gas responsiveness across flow rates and FiO₂ (fraction of inspired oxygen) inputs. RSV-NE displayed strong antioxidant activity and concentration-dependent inhibition of free radicals. RSV-NE maintained higher cell viability and prevented RAS-selective lethal compound 3 (RSL3)-induced ferroptosis in murine macrophages (macrophage cell line RAW 264.7), compared to the free RSV solution. Morphological and functional protection against RSL3-induced ferroptosis was confirmed microscopically. Conclusions: This study establishes a robust and scalable PFC-NE platform integrating antioxidant and oxygen delivery, along with NIRF-based non-invasive live monitoring of organ perfusion during machine-supported preservation. These combined features position PFC-NE as a promising next-generation acellular perfusate for preventing IRI and improving graft viability during ex vivo machine perfusion. Full article

In semiconductor manufacturing, fluorinated gases such as CHF₃ and CH₂F₂ are widely used as process gases for plasma etching and cleaning. However, their decomposition within the plasma environment leads to the formation of secondary fluorinated by-products with high global warming potential (GWP). Understanding how plasma intensity affects the generation characteristics of these by-products under realistic process conditions is essential for developing country-specific emission factors and improving inventory accuracy. This study analyzes the by-product formation behavior of CHF₃ and CH₂F₂ under three plasma power conditions (500 W, 600 W, and 700 W), based on process data representative of domestic semiconductor facilities. The quantitative analysis revealed distinct reaction trends between the two gas systems. In the CHF₃ process, a reaction-pathway bifurcation was observed at 700 W, where the formation of high-GWP perfluorocarbons (PFCs, e.g., CF₄, C₂F₆) decreased, while the production of low-GWP fluorinated compounds such as C₄F₆ increased, resulting in an overall 18% reduction in CO₂eq. emissions. Conversely, CH₂F₂ showed a continuous increase in fluoromethane (CH₃F) generation with higher plasma power due to the higher hydrogen content in its molecular structure, leading to an 18.4% net reduction in total GWP emissions. These results provide scientific evidence for understanding the relationship between plasma intensity and by-product formation in fluorinated gas systems under conditions relevant to the Korean semiconductor industry, and offer a foundation for improving national F-gas emission factor development. Full article

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Background/Objectives: While the presence of inflammatory processes in stenotic aortic valves is acknowledged, no systematic characterization of the systemic immune reaction upon aortic valve stenosis (AS) has been performed yet. The hypothesis of this study was that AS induces a systemic inflammatory reaction linked with local processes in the heart. Methods: Murine wire injury (WI) to induce AS, or sham surgery, were performed prior to the 4-week assessment of AS severity, left ventricular (LV) function and hypertrophy with echocardiography (echo). Organ weights, levels of leukocytes, cytokines and costimulatory molecules in blood, heart, and peripheral immune organs (spleen, liver, lymph nodes), and immune cell uptake of Cy5-labelled perfluorocarbon nanoemulsions were measured. Results: Trends towards correlation were found between organ weights, myocardial immune cells and echo. Cytokine mRNA levels trended mainly towards an increase in heart and regional lymph nodes and a reduction in spleen and liver, and correlation with echo was more homogeneous after WI. Unchanged cytokine protein levels in myocardium and plasma trended to correlate with echo. A homogeneous pattern was found for echo and costimulatory molecule correlation, while PFC uptake by lymphatic cells was reduced upon AS. Conclusions: The results suggest a link between number and activation state of leukocytes in peripheral organs and cardiac processes in AS. Considering the pathological value of inflammation, it is crucial that future studies investigate if a modulation of the systemic inflammatory reaction relieves severity of AS and opposes development of heart failure. Full article

Lipase production by the strictly aerobic yeast Yarrowia lipolytica is closely related to the content of dissolved oxygen in the culture medium. Some strategies to improve oxygen transfer to microorganisms have already been used, such as the use of perfluorocarbons (PFCs). The present work investigates the influence of agitation speed and the use of perfluorodecalin (PFC) on the profile of the produced lipases. Lipase production increased 2.5-fold with a higher agitation speed (550 to 650 rpm) without PFCs in the medium. The presence of an oxygen carrier led to a significant 91% increase in lipase production at lower shaking speeds compared to the assay without PFC; however, an increase in lipase production was not detected with PFC at 650 rpm. The protein profiles exhibited typical bands for two lipases produced (near 40 and 60 kDa), and these bands became more intense when PFC was added during production, as a result of the large enhancement in lipolytic activity. Additionally, the protein profiles obtained from extracts at 650 rpm were clearer and more selective regardless of the presence of PFC, suggesting an enhancement in specific activity associated with increased shaking. These findings highlight the significant impact of oxygen availability on lipase production, offering valuable insights for industrial applications. Full article

In situ measurements of the chemical identity and quantity of anode gases during electrochemical measurements and rare earth (RE) electrolysis from fluoride-based molten salts composed of different kinds of rare earth oxides (REOs) were performed using FTIR spectrometry. Linear sweep voltammetry (LSV) was carried out to characterize oxidation processes and determine the anodic effect from NdF₃ + PrF₃ + LiF + REO melt. RE complex formation and subsequent reactions on the GC anode surface were discussed to understand the formation pathways of CO/CO₂ and perfluorocarbon gases (PFC), mainly CF₄ and C₂F₆. The LSV shows that increasing the REO content from 1 wt.% up to 4 wt.% in the system, leads to a positive shift in the critical potential for a full anode effect, recorded around 4.50 V vs. W with 4 wt.% REO. The FTIR results from on-line off-gas analysis during LSV measurements indicate that the anode gas products were composed mainly of CO and CO₂, whereas CF₄ can be detected before the full anode effect and C₂F₆ at and after this phenomenon. Compositions of off-gases from electrolysis performed using different kinds of REOs were compared. The main off-gas component was found to be CO in RE electrolysis with REOs as raw materials, while in electrolysis with magnet recycling derived oxides (MRDOs), CO₂ content was slightly higher compared to CO. PFC emissions during RE electrolysis were generally similar: CF₄ was detected periodically, but in negligible concentrations, while C₂F₆ was not detected. Full article

Nanomedicine holds great potential for revolutionizing medical treatment. Ongoing research and advancements in nanotechnology are continuously expanding the possibilities, promising significant advancements in healthcare. To fully harness the potential of nanotechnology in medical applications, it is crucial to conduct safety evaluations for the nanomedicines that offer effective benefits in the preclinical stage. Our recent efficacy studies indicated that rapamycin perfluorocarbon (PFC) nanoparticles showed promise in mitigating cisplatin-induced acute kidney injury (AKI). As cisplatin is routinely administered to ovarian cancer patients as their first-line chemotherapy, in this study, we focused on evaluating the safety of rapamycin PFC nanoparticles in mice bearing ovarian tumor xenografts. Specifically, this study evaluated the effects of repeat-dose rapamycin PFC nanoparticle treatment on vital organs, the immune system, and tumor growth and assessed pharmacokinetics and biodistribution. Our results indicated that rapamycin PFC nanoparticle treatment did not cause any detectable adverse effects on cardiac, renal, or hepatic functions or on splenocyte populations, but it reduced the splenocyte secretion of IL-10, TNFα, and IL12p70 upon IgM stimulation. The pharmacokinetics and biodistribution results revealed a significant enhancement in the delivery of rapamycin to tumors by rapamycin PFC nanoparticles, which, in turn, led to a significant reduction in ovarian tumor growth. Therefore, rapamycin PFC nanoparticles have the potential to be clinically beneficial in cisplatin-treated ovarian cancer patients. Full article

“Hot spot” ¹⁹F magnetic resonance imaging (MRI) has garnered significant attention recently for its ability to image various disease markers quantitatively. Unlike conventional gadolinium-based MRI contrast agents, which rely on proton signal modulation, ¹⁹F-MRI’s direct detection has a unique advantage in vivo, as the human body exhibits a negligible background ¹⁹F-signal. However, existing perfluorocarbon (PFC) or PFC-based contrast materials suffer from several limitations, including low longitudinal relaxation rates and relatively low imaging efficiency. Hence, we designed a macromolecular contrast agent featuring a high number of magnetically equivalent ¹⁹F-nuclei in a single macromolecule, adequate fluorine nucleus mobility, and excellent water solubility. This design utilizes superfluorinated polyphosphazene (PPz) polymers as the ¹⁹F-source; these are modified with sodium mercaptoethanesulfonate (MESNa) to achieve water solubility exceeding 360 mg/mL, which is a similar solubility to that of sodium chloride. We observed substantial signal enhancement in MRI with these novel macromolecular carriers compared to non-enhanced surroundings and aqueous trifluoroacetic acid (TFA) used as a positive control. In conclusion, these novel water-soluble macromolecular carriers represent a promising platform for future MRI contrast agents. Full article

Phase-change nanodroplets (PCND;NDs) are emulsions with a perfluorocarbon (PFC) core that undergo acoustic vaporisation as a response to ultrasound (US). Nanodroplets change to microbubbles and cavitate while under the effect of US. This cavitation can apply forces on cell connections in biological barrier membranes, such as the blood–brain barrier (BBB), and trigger a transient and reversible increased permeability to molecules and matter. This study aims to present the preparation of lipid-based NDs and investigate their effects on the brain endothelial cell barrier in vitro. The NDs were prepared using the thin-film hydration method, followed by the PFC addition. They were characterised for size, cavitation (using a high-speed camera), and PFC encapsulation (using FTIR). The bEnd.3 (mouse brain endothelial) cells were seeded onto transwell inserts. Fluorescein with NDs and/or microbubbles were applied on the bEND3 cells and the effect of US on fluorescein permeability was measured. The Live/Dead assay was used to assess the BBB integrity after the treatments. Size and PFC content analysis indicated that the NDs were stable while stored. High-speed camera imaging confirmed that the NDs cavitate after US exposure of 0.12 MPa. The BBB cell model experiments revealed a 4-fold increase in cell membrane permeation after the combined application of US and NDs. The Live/Dead assay results indicated damage to the BBB membrane integrity, but this damage was less when compared to the one caused by microbubbles. This in vitro study shows that nanodroplets have the potential to cause BBB opening in a similar manner to microbubbles. Both cavitation agents caused damage on the endothelial cells. It appears that NDs cause less cell damage compared to microbubbles. Full article

Antiangiogenic therapy with sorafenib (SF) alone is ineffective in eradicating tumors, and its long-term application can exacerbate tumor hypoxia, which in turn restricts SF’s therapeutic efficacy. Here, a redox-responsive fluorinated peptide (DEN-TAT-PFC) consisting of dendritic poly-lysine, cell-penetrating peptide TAT, and perfluorocarbon was designed and synthesized to co-load siRNA-targeting hypoxia-inducible factors (siHIF-1α) and SF. The unique architecture of the peptide and fluorinated modifications enhanced the siRNA delivery efficiency, including increased siRNA binding, GSH-responsive release, cellular uptake, endosomal escape, and serum resistance. Simultaneously, the DEN-TAT-PFC/SF/siHIF-1α co-delivery system achieved efficient knockdown of HIF-1α at mRNA and protein levels, thus alleviating hypoxia and further substantially reducing VEGF expression. Additionally, the excellent oxygen-carrying ability of DEN-TAT-PFC may facilitate relief of the hypoxic microenvironment. As a result of these synergistic effects, DEN-TAT-PFC/SF/siHIF-1α exhibited considerable anti-tumor cell proliferation and anti-angiogenesis effects. Therefore, DEN-TAT-PFC can be a versatile platform for fabricating fluorine-containing drugs/siRNA complex nano-systems. Full article

Heptafluoropropyl methyl ether (HFE-347mcc3), as a lower-GWP (global warming potential) alternative to PFCs (perfluorocarbons), was used to etch SiO₂ contact holes. The etch profiles of the SiO₂ contact holes in HFE-347mcc3/O₂/Ar plasmas showed more bowing at lower flow rate ratios of HFE-347mcc3 to Ar, whereas more narrowing occurred at higher ratios. The measurements of the angular dependences of the deposition rates of fluorocarbon films on the surface of SiO₂ and the etch rates of SiO₂ showed that the shape evolution of contact-hole etch profiles at different HFE-347mcc3/Ar ratios was attributed to an increase in etch resistance and a decrease in etch ability of the sidewalls of the contact hole with the increasing HFE-347mcc3/Ar ratio. This resulted in determining the optimum ratio of HFE-347mcc3 to Ar to achieve the maximum anisotropy of the contact hole etched in HFE-347mcc3/O₂/Ar plasmas. By carefully selecting the specific flow rates of HFE-347mcc3/O₂/Ar (9/2/19 sccm), a highly anisotropic and bowing-free SiO₂ contact hole, with a 100 nm diameter and an aspect ratio of 24, was successfully achieved. Full article

This paper proposes the use of environmentally friendly alternatives, C₆F₆ and C₄H₂F₆, as perfluorocarbon (PFC) and hydrofluorocarbon (HFC) precursors, respectively, for SiO₂ plasma etching, instead of conventional precursors C₄F₈ and CHF₃. The study employs scanning electron microscopy for etch profile analysis and quadrupole mass spectrometry for plasma diagnosis. Ion bombardment energy at the etching conditions is determined through self-bias voltage measurements, while densities of radical species are obtained using quadrupole mass spectroscopy. The obtained results compare the etch performance, including etch rate and selectivity, between C₄F₈ and C₆F₆, as well as between CHF₃ and C₄H₂F₆. Furthermore, greenhouse gas (GHG) emissions are evaluated using a million metric ton of carbon dioxide equivalent, indicating significantly lower emissions when replacing conventional precursors with the proposed alternatives. The results suggest that a significant GHG emissions reduction can be achieved from the investigated alternatives without a deterioration in SiO₂ etching characteristics. This research contributes to the development of alternative precursors for reducing global warming impacts. Full article

Perfluorocarbon nanodroplets (PFCnDs) are sub-micrometer emulsions composed of a surfactant-encased perfluorocarbon (PFC) liquid and can be formulated to transiently vaporize through optical stimulation. However, the factors governing repeated optical droplet vaporization (ODV) have not been investigated. In this study, we employ high-frame-rate ultrasound (US) to characterize the ODV thresholds of various formulations and imaging parameters and identify those that exhibit low vaporization thresholds and repeatable vaporization. We observe a phenomenon termed “preconditioning”, where initial laser pulses generate reduced US contrast that appears linked with an increase in nanodroplet size. Variation in laser pulse repetition frequency is found not to change the vaporization threshold, suggesting that “preconditioning” is not related to residual heat. Surfactants (bovine serum albumin, lipids, and zonyl) impact the vaporization threshold and imaging lifetime, with lipid shells demonstrating the best performance with relatively low thresholds (21.6 ± 3.7 mJ/cm²) and long lifetimes (t_1/2 = 104 ± 21.5 pulses at 75 mJ/cm²). Physiological stiffness does not affect the ODV threshold and may enhance nanodroplet stability. Furthermore, PFC critical temperatures are found to correlate with vaporization thresholds. These observations enhance our understanding of ODV behavior and pave the way for improved nanodroplet performance in biomedical applications. Full article

The emission of air pollutants weakens the body’s immune system and can increase the prevalence of coronaviruses. This study examined the effects of six environmental pollutant gases, including Carbon Dioxide (CO2), Methane (CH4), Nitrous Oxide (N2O), Hydrofluorocarbons (HFC), Perfluorocarbons (PFC), and Sulphur Hexafluoride (SF6), on the prevalence of coronaviruses (i.e., coronavirus cases, total deaths, and active cases) in 30 European countries. Due to the benefits of ridge regression, this method was used to investigate the effects of those environmental pollutants on coronavirus cases. The results showed that all six gases had a positive effect on active coronavirus cases in European countries. This study concludes that industrialized European countries could focus on reducing environmental pollutants to decrease the effects of future pandemics. Full article