Synthetic circRNA therapeutics: innovations, strategies, and future horizons

MedComm, Journal Year: 2024, Volume and Issue: 5(11)

Published: Nov. 1, 2024

Abstract Small molecule drugs are increasingly emerging as innovative and effective treatments for various diseases, with mRNA therapeutics being a notable representative. The success of COVID‐19 vaccines has underscored the transformative potential in RNA therapeutics. Within family, there is another unique type known circRNA. This single‐stranded closed‐loop offers advantages over mRNA, including enhanced stability prolonged protein expression, which may significantly impact therapeutic strategies. Furthermore, circRNA plays pivotal role pathogenesis such cancers, autoimmune disorders, cardiovascular making it promising clinical intervention target. Despite these benefits, application settings remains underexplored. review provides comprehensive overview current state synthetic therapeutics, focusing on its synthesis, optimization, delivery, diverse applications. It also addresses challenges impeding advancement from bench to bedside. By summarizing aspects, aims equip researchers insights into ongoing developments future directions Highlighting both progress existing gaps research, this valuable perspectives advancing field guiding investigations.

Language: Английский

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Photoresponsive Drug Delivery Systems: Challenges and Progress

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(38)

Published: June 12, 2024

Abstract Photoresponsive drug delivery systems (PDDSs) have emerged as a promising toolbox for delivery, offering precise control over the site, duration, and dosage of light‐triggered medication. It allows controlled release, photo‐triggered targeting, diagnosis, treatment, improving precision efficacy therapies various diseases. Despite progress in designing different PDDSs, clinical translation has been limited due to obstacles. Herein, this review article focuses on three critical challenges PDDSs: 1) accumulation at diseased lesions, 2) light irradiation, 3) penetration tissues. Also, summarizes discusses current advancements strategies address these challenges. Overall, it emphasizes need clarify from bench bedside develop enhance therapeutic outcomes, increase compatibility patient compliance, unlock possibilities therapies.

Language: Английский

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Numerical modeling of ultrasound propagation in the inner ear for sonoporation-mediated drug delivery

Applied Physics Letters, Journal Year: 2025, Volume and Issue: 126(2)

Published: Jan. 13, 2025

To date, no treatment has been developed for targeted delivery to the inner ear (IE). Sonoporation, a promising drug method, increases permeability of round window membranes (RWMs), enhancing diffusion IE. A dedicated ultrasound protocol is essential treat IE pathologies in combination with sonoporation. In situ acoustic pressure (AP) measurements cannot be used RWM sonoporation because heterogeneous anatomy temporal bone. This study aimed model propagation ensure adequate AP The impact position probe relative on as well potential temperature caused by tissue/ultrasound interaction were investigated. Using MATLAB®, surgical procedure was simulated based computed tomography scans sheep heads (14 IEs). An (12.7 mm diameter, 1 MHz) degassed water-filled adapter placed front RWM. Mechanical properties, such tissue density, sound speed, and attenuation, computed. Ultrasound using k-wave. Standing waves can double locally; however, final comparable free water field map when accounting microbubble-induced attenuation. angle distance have minimal effect AP; main centering No significant thermal elevation observed. computational paves way designing an optimal safe sonoporation-mediated into

Language: Английский

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The Compression-Dominated Ultrasound Response of Poly(n-butyl cyanoacrylate) Hard-Shelled Microbubbles Induces Significant Sonoporation and Sonopermeation Effects In Vitro

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

The process of locally increasing the permeability cell membranes or layers is referred to as sonoporation sonopermeation, respectively, and opens up perspectives for drug delivery in cancer treatment by facilitating enhanced local accumulation. These effects are mediated ultrasound-activated microbubbles close proximity cells. Here, selection ultrasound settings according intended effect on biological tissue remains a challenge, especially broadly size-distributed microbubbles, which show heterogeneous response ultrasound. For this purpose, we have analyzed general narrower poly(n-butyl cyanoacrylate) hard-shelled via ultra-high-speed imaging evaluated their ability stimulate sonopermeation vitro compared lipid soft-shelled microbubbles. Ultra-high-speed revealed either compression-dominated compression-only at peak negative acoustic pressures higher than 165 kPa an onset bursting 500 kPa. experiments demonstrated that induced significant effects, also when only compressing 300 neagtive pressure. Compared were less prominent, was attributed differences responses size distributions. This validation qualifies them future vivo applications, would benefit from narrow distribution, thereby allowing more control therapeutic suitably adjusting parameters.

Language: Английский

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Recent advances in smart biomaterials based on ultrasonic effects

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 160524 - 160524

Published: Feb. 1, 2025

Language: Английский

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Inhibition of Thioredoxin-Reductase by Auranofin as a Pro-Oxidant Anticancer Strategy for Glioblastoma: In Vitro and In Vivo Studies

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2084 - 2084

Published: Feb. 27, 2025

Reactive oxygen species (ROS) play a key role in cancer progression and antitumor therapy. Glioblastoma is highly heterogeneous tumor with different cell populations exhibiting various redox statuses. Elevated ROS levels cells promote growth simultaneously make them more sensitive to anticancer drugs, but further elevation leads death apoptosis. Meanwhile, subsets of cells, such glioblastoma stem (GSC) or the microenvironment (TME), demonstrate adaptive mechanisms excessive production by developing effective antioxidant systems as glutathione- thioredoxin-dependent. GSCs higher chemoresistance lower than other glioma while TME create pro-oxidative environment have immunosuppressive effects. Both subpopulations become an attractive target for therapies. Increased expression thioredoxin reductase (TrxR) often associated poor patient survival. Various TrxR inhibitors been investigated potential therapies, including nitrosoureas, flavonoids metallic complexes. Gold derivatives are irreversible TrxR. Among them, auranofin (AF), selective inhibitor, has proven its effectiveness drug treatment rheumatoid arthritis efficacy agent demonstrated preclinical studies vitro vivo. However, clinical application AF could be challenging due low solubility insufficient delivery glioblastoma. Different strategies hydrophobic drugs used increase concentration brain. Combining therapeutic approaches that affect status new strategy treating brain diseases.

Language: Английский

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Improving the Efficiency of Ultrasound and Microbubble Mediated Gene Delivery by Manipulation of Microbubble Lipid Composition

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Ultrasound and microbubble-mediated gene delivery is emerging as a powerful nonviral approach due to its ability target various tissues. Since microbubble cavitation plays crucial role in delivery, factors affecting cavitation, such composition, size, ultrasound pressure, frequency, pulse interval, can directly affect the efficiency of delivery. The effect parameters on has been systematically investigated numerous studies. However, relatively few studies have influence different compositions In this paper, we report that microbubbles made with same lipids but poly(ethylene glycol) (PEG) derivatives lead significantly efficiencies vitro. Moreover, show type PEG derivative used formulations greatly influences acoustic response (i.e., resonance frequency frequency-dependent attenuation coefficient), thus explaining differences efficiencies. Our results highlight changing single component formulation, i.e., derivative, improve by 3-fold. This comparative study may help researchers designing for optimal

Language: Английский

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Harnessing the oloid shape in magnetically driven robots to enable high-resolution ultrasound imaging

Science Robotics, Journal Year: 2025, Volume and Issue: 10(100)

Published: March 26, 2025

Magnetic fields enable remote manipulation of objects and are ideal for medical applications because they pass through human tissue harmlessly. This capability is promising surgical robots, allowing navigation deeper into the anatomy accessing organs beyond reach current technologies. However, magnetic typically limited to a maximum two–degrees-of-freedom orientation, restricting complex motions, especially those including rolling around main axis robot. To address this challenge, we introduce robot design inspired by embodied intelligence unique geometry developable rollers, leveraging oloid shape. The oloid, with its axial asymmetry sinusoidal motion, facilitates when precisely controlled an external field. We present versatile closed-loop control model ensure precise oloid-shaped was validated in endoluminal integration 28-megahertz micro-ultrasound array perform virtual biopsies, noninvasive real-time histological imaging. Extensive vitro vivo tests using porcine showed robot’s ability execute sweeping identify lesions, generate detailed three-dimensional scans gastrointestinal subsurface tissue. research not only restores critical movement robots but also enables additional clinical deep within body.

Language: Английский

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Development of a dual-frequency sonophoresis for enhanced skin permeability and efficient drug delivery

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125539 - 125539

Published: March 1, 2025

Language: Английский

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Controlling microbubble formation in microfluidic devices: Advancements in experimental, theoretical, and numerical strategies

Applied Physics Reviews, Journal Year: 2025, Volume and Issue: 12(2)

Published: April 7, 2025

Microfluidic devices are becoming increasingly popular for producing microbubbles, as these provide much greater control over microbubble size compared to traditional methods such sonication and amalgamation. Recent developments in microfabrication technologies have prompted several modifications conventional microfluidic devices, which allow one “engineer” microbubbles relevant specific biomedical applications. The pursuit of improvements engineering requires a detailed understanding fluid flow behavior systems, is where the motivation this work originates from. This provides an extensive review theoretical, experimental, numerical investigations reported literature understand formation using devices. evolution gas–liquid interfaces during formation, pinch-off mechanism, confinement effect on production rate been discussed. scaling laws prediction diameter regimes maps providing details about interplay different forces also reviewed. Furthermore, CFD simulations based interface tracking schemes along with recent strategies upscale We conclude by outlining need current systems produce can pave way new research field microfluidics engineering.

Language: Английский

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