Search Results (17,429)

Both basic and preclinical research, as well as the development of new therapies, require tools that allow for the selective labelling of specific cell types and the targeted delivery of drugs. The developed tools must then be validated in biological systems. In view of the lack of effective therapies for many neurodevelopmental disorders, including neonatal brain injuries, we decided to use the newly described, innovative SPAchips^® (a4cell, Pozuelo de Alarcón, Spain) tool and test it in labelling neonatal rat neural cells. In our studies, rat primary cultures of neurons and glial cells (astrocytes, oligodendrocytes, and microglia) were incubated with different concentrations of SPAchips^®. At selected time points, uptake of the tested microchips by particular cell types was assessed using lineage-specific antibodies and visualized using a confocal microscope. Additionally, the potential cytotoxicity of added microparticles was verified, as was the possibility of microglia activation. The study indicates that the tested microdevices selectively label neonatal rat microglia and can be a useful tool for visualizing this cell type, as well as a non-toxic tool for developing innovative strategies based on the functionalization of microparticles aimed at modulating neuroinflammatory processes. Full article

Background/Objectives: The present work deals with the sol–gel synthesis of hybrid materials based on a silica–polyvinylpyrrolidone (Si-PVP) system. Methods: The nanohybrids have been prepared using an acidic catalyst at ambient temperature. Ibuprofen (IBP) was used as a model substance in the obtained model drug systems, while tetraethyl orthosilicate (TEOS) was used as a silica precursor. Poly(vinylpyrrolidone) (PVP) and IBP were introduced into the reaction mixture as solutions in ethanol using two different approaches: (i) a direct introduction of a drug solution into the reaction mixture during sol–gel synthesis, and (ii) a solvent deposition technique. Results: XRD data provide evidence that IBP entrapped in the silica–PVP network is in an amorphous state. By SEM it was revealed that in the adsorbate, the IBP particles possess an average particle size of about 20 μm. Based on the obtained IR and UV-Vis spectral results, the existence of hydrogen bonding of IBF with silica and PVP could be suggested. Solid-state NMR analysis allowed the identification of the presence of both crystalline-like and amorphous phases in the hybrid material prepared by the sol–gel method, while it was demonstrated that in the adsorbate, the rigid crystalline dimeric structure of the drug has been preserved. Conclusions: The overall analysis of the structural characteristics of the two materials indicated that in the hybrid material obtained by the sol–gel method, the interactions between the amorphous drug, PVP, and the silica matrix are more pronounced as compared to the adsorbate. An improvement of the drug’s aqueous solubility as well of in vitro drug release profile (up to 8 h) was achieved, demonstrating the potential of the developed drug–silica–organic polymer nanohybrid as a promising drug delivery system. Full article

Currently, there is a growing interest in biomedical research in the use of inorganic nanoparticles for targeted drug delivery, as biosensors, and in theranostic applications. This review examines the interaction of inorganic nanoparticles with protein molecules depending on the chemical nature, size, and surface charge of the nanoparticles. The effect of protein and nanoparticle concentration, as well as their incubation time, is analyzed. The work focuses on the influence of parameters such as pH, ionic strength, and temperature on the interaction of nanoparticles with protein molecules. The following dependencies were studied in detail: the thickness of the protein corona as a function of nanoparticle size; the size of nanoparticles after interaction with protein as a function of protein and nanoparticle concentration; the distribution of zeta potentials in colloids of nanoparticles, proteins, and their mixtures. It has been shown that proteins and nanoparticles can influence each other’s physicochemical properties. This can lead to the emergence of new biological properties in the system. Therefore, the adsorption of proteins onto nanoparticle surfaces can induce conformational changes. The probability of changing the protein structure increases when a covalent bond is formed between the nanoparticle and the protein molecule. Studies demonstrate that protein structure remains more stable with spherical nanoparticles than with rod-shaped or other high-curvature nanostructures. The results presented in the review demonstrate the possibility of adapting physiological responses to nanomaterials by changing the chemical composition of the surface of nanoparticles and their size and charge. Full article

Cancer is a major challenge to global health, and its incidence rate and mortality are expected to continue to rise in the coming decades. Traditional treatment methods such as surgery, radiotherapy, and chemotherapy have limitations, which has prompted people to explore new treatment strategies. As a promising therapeutic approach, oncolytic viruses can selectively target and lyse tumor cells while avoiding damage to normal tissues. This article systematically reviews the mechanisms by which oncolytic viruses induce various forms of cell death, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. We explored the direct killing effect of oncolytic viruses and their ability to activate local and systemic antitumor immunity, with a focus on the latest developments in the clinical application of oncolytic viruses, such as the development of novel recombinant viruses. In addition, we also analyzed strategies to enhance the efficacy of oncolytic viruses through gene modification, combination therapy, and targeted delivery systems. A deeper understanding of the multiple mechanisms of action of oncolytic viruses can help us develop more effective and personalized cancer treatment plans. Future research should focus on optimizing oncolytic viruses to overcome tumor drug resistance and improve patient prognosis, making them an important pillar of cancer treatment. Full article

RNA-based therapeutics offer transformative potential for treating devastating diseases. However, current RNA delivery technologies face significant hurdles, including inefficient tissue targeting, insufficient selectivity, and severe side effects, leading to the termination of many clinical trials. This review critically assesses the landscape of RNA-derived medicines, examining world-renowned mRNA vaccines (Spikevax, BNT162b2/Comirnaty) and RNA-based therapeutics like Miravirsen (anti-miR-122). It details the composition and clinical trial results of numerous modified short RNA drugs (e.g., siRNAs, miRNA mimetics/inhibitors) targeting various conditions. Prospects for RNA-based medicines are analysed for diseases with substantial societal impact, such as cancer, autoimmune disorders, and infectious diseases, with a focus on evolving delivery methods, including lipid nanoparticles, viral vectors, and exosomes. RNA-mediated macrophage reprogramming emerges as a promising strategy, potentially enhancing both delivery and clinical efficacy. This review highlights that while approved RNA therapies primarily target rare diseases due to delivery limitations, novel approaches in RNA modification, targeted delivery systems, and enhanced understanding of molecular mechanisms are crucial for expanding their application to prevalent diseases and unlocking their full therapeutic potential. Full article

This review provides a comprehensive overview of the therapeutic potential of omaveloxone (OMA) for the treatment of Friedreich’s ataxia (FA), along with an analysis of the historical development and current status of the synthetic strategies for OMA production. OMA activates the nuclear factor-2-(erythroid-2)-related (Nrf2) pathway in vitro and in vivo, in both animal models and humans. The Nrf2 pathway plays a crucial role in the cellular response to oxidative stress. Furthermore, OMA has been shown to mitigate mitochondrial dysfunction, restore redox homeostasis and downregulate nuclear factor-κB (NF-κB), a key mediator of inflammatory responses. Through these mechanisms, OMA contributes to tissue protection and inflammation reduction in patients with FA. The review also highlights future perspective, focusing on the challenges associated with OMA reprofiling through innovative drug delivery approaches and its potential repurposing for diseases beyond FA. Full article

Chitosan-based nanoparticles were prepared using an eco-friendly chemical procedure that conjugates natural fatty acids to the backbone of chitosan. This consists of reacting two molecules in the absence of a solvent and using microwaves to promote the chemical transformation. Both conditions make the whole chemical process more eco-compatible in terms of reagents and energy consumption. The chemical structure and the self-association behavior of chitosan–fatty acid conjugates were characterized by FT-IR, NMR, and dynamic light scattering. The conjugates displayed an enhanced solubility and efficient self-assembly in aqueous solution. The antimicrobial activity of the resulting nanoparticles was evaluated against Escherichia coli (Gram-negative) and Bacillus subtilis (Gram-positive). The micelles significantly inhibited E. coli growth (35–60%), even at relatively low concentrations, whereas negligible activity was observed against B. subtilis. The antibacterial efficacy appears to arise primarily from the ability of the developed nanostructured conjugates to perturb bacterial membranes. These results support the potential of chitosan–fatty acid conjugates as sustainable nanomaterials for biomedical applications, particularly as eco-friendly antimicrobial agents. Future work will evaluate their activity against other Gram-positive pathogens and explore their use in drug delivery. Full article

Oleosomes are submicron oil bodies of a triacylglycerol core enveloped by a phospholipid monolayer and embedded proteins, forming a naturally assembled nanocarrier with exceptional oxidative resilience, interfacial stability, and biocompatibility. Their unique architecture supports solvent-free extraction, self-emulsification, and near-complete encapsulation of highly lipophilic compounds (log P > 4), including curcumin and cannabidiol, with reported efficiencies exceeding 95%. These plant-derived droplets enhance oral bioavailability through lymphatic uptake and enable targeted delivery strategies such as magnetically guided chemotherapy, which has reduced tumor burden by approximately 70% in vivo. The review critically examines recent advances in oleosome research, spanning botanical sourcing, green extraction technologies, interfacial engineering, xenobiotic encapsulation, pharmacokinetics, and therapeutic applications across oncology, dermatology, metabolic disease, and regenerative medicine. Comparative analyses demonstrate that oleosomes rival or surpass synthetic lipid nanocarriers in encapsulation efficiency, oxidative stability, and cost efficiency while offering a sustainable, clean-label alternative. Remaining challenges, including low loading of hydrophilic drugs, allergenicity, and regulatory standardization, are addressed through emerging strategies such as hybrid oleosome–liposome systems, recombinant oleosin engineering, and stimulus-responsive coatings. These advances position oleosomes as a versatile and scalable platform with significant potential for food, cosmetic, and pharmaceutical applications. Full article

Hearing loss is a major health burden, often caused by ototoxic drugs such as cisplatin and gentamicin. Effective therapy is limited by the poor penetrability of drugs into inner ear compartments. This study aimed to develop and test magnetic cationic liposomes as nanocarriers for targeted corticosteroid delivery to auditory hair cells. Carboxymethyl chitosan–coated liposomes were prepared by the lipid film hydration method, incorporating magnetic nanoparticles and dexamethasone phosphate in their aqueous core. The optimal liposomal formulation, in terms of size, zeta potential, and drug leakage over time, was selected and tested in an in vitro model of drug-induced ototoxicity. HEI-OC1 cells exposed to cisplatin or gentamicin were co-treated with the liposomal formulations, and viability, mitochondrial membrane potential, and β-galactosidase activity were assessed. The results demonstrated that magnetic, polymer-coated liposomes protected against cytotoxicity by preserving mitochondrial function and significantly reducing senescence. These findings provide a proof of concept for magnetically responsive liposomal systems as potential therapeutic platforms for preventing or treating drug-associated hearing loss. Full article

Background/Objectives: Understanding the interactions between nanoparticles and mucosal tissues is crucial for the development of advanced drug delivery systems, as the diffusion behavior of nanoparticles through mucus is strongly influenced by their size and surface properties, and the viscoelastic nature of the hydrogel matrix. In this study, we investigated the impact of nanoparticle size, surface charge, and hydrogel crosslinking density on nanoparticle diffusion in a mucus model in vitro. Method: Citrate-stabilized and PEGylated 30 and 100 nm gold nanoparticles were used as a model of nanoparticle and their diffusion through mucus-mimicking mucin-based hydrogels of two different crosslinking densities was assessed. Results: Citrate-stabilized 30 nm nanoparticles demonstrated greater diffusion in hydrogels mimicking native mucus compared to more densely crosslinked ones, reaching approximately 50.3 ± 0.2% diffusion within the first 5 min of the assay. This size-dependent effect was not observed for the 100 nm citrate-stabilized nanoparticles, which showed limited diffusion in both hydrogel types. To confer different surface charge, gold nanoparticles were functionalized by the conjugation of poly(ethylene glycol) (PEG) derivatives of identical molecular weight with different terminal moieties (neutral, and positively and negatively charged) to modulate the surface charge and assess their interaction with the negatively charged mucin matrix. PEGylated particles exhibited significantly greater mobility than their citrate-stabilized counterparts, regardless of size or hydrogel density owing to the muco-penetration effect of PEG. Among PEGylated particles, the neutral and negatively charged 30 nm variants demonstrated higher diffusion than the positively charged ones due to weaker interactions with the negatively charged mucin hydrogel. For the 100 nm particles, the neutral PEGylated nanoparticles exhibited greater diffusion than their positively charged counterparts. Conclusions: Overall findings could provide valuable insights into the more rational design of nanoparticle-based drug delivery systems targeting mucosal tissues. Full article

Oxaliplatin is an anticancer drug used to treat colorectal and gastric cancers. In many cases, chemotherapy is discontinued due to adverse events caused by anticancer drugs. To address this challenge, we developed a sustained-release drug delivery system using polycaprolactone sheets embedded with oxaliplatin (oxaliplatin sheets) and evaluated their therapeutic potential in murine models of colon and gastric cancers. Antitumor efficacy was compared with conventional intraperitoneal administration by monitoring tumor volume, body weight, and systemic oxaliplatin concentrations over 21 days, along with histopathological assessment of tumors and hepatic tissue. Oxaliplatin sheets demonstrated superior tumor suppression, significantly reduced Ki-67 positivity, and mitotic indices. Additionally, antitumor effects and blood oxaliplatin levels were consistent regardless of implantation site. Notably, oxaliplatin sheets significantly decreased weight loss compared with intraperitoneal administration. In our analysis of liver pathology, we found that hepatic sinusoidal obstruction and hepatocellular degeneration were significantly increased after intraperitoneal administration compared with untreated mice and mice treated with oxaliplatin sheets. Furthermore, treatment with oxaliplatin sheets improved survival. Thus, our oxaliplatin sheets exhibited effective tumor control and reduced side effects, indicating their potential as a promising treatment for advanced gastric and colorectal cancers. Full article

Octominin is a peptide derived from the Octopus minor defense protein, which has shown antimicrobial and immunomodulatory properties. The present study describes the efficacy of Octominin-encapsulated chitosan (CN) nanoparticles (Octominin-CNPs) on in vitro and dermal wound healing in zebrafish. Initial viability analysis revealed there was no significant toxicity of Octominin-CNPs up to 200 μg/mL in human dermal fibroblast (HDF) cells and in zebrafish larvae (up to 50 μg/mL). Moreover, the potential wound healing activity of Octominin-CNPs was observed using the cell-scratch assay. In the in vivo study, wounded adult zebrafish were applied with the appropriate treatment (PBS, CNPs, Octominin, and Octominin-CNPs) 20 μg/wound/fish as a topical application at 0, 2, and 4 days post-wounding (dpw) while photographs of each wound site were taken at 2, 4, 7, 10, 14, and 21 dpw, and surface area was measured using ImageJ software (Ver. 1.8.0, NIH, Bethesda, MD, USA) to calculate the wound healing percentage (WHP) and wound healing rate (WHR). From the observed results, at 4 dpw, all treatments showed a negative impact on wound healing, where the lowest WHR and the WHP were given by the negative control (NC) until the 14th day. After 7 dpw, all fish except the NC showed increased wound healing activity. Compared to the Octominin, the Octominin-CNPs showed higher activity, which was at its peak on 21 dpw. Furthermore, Octominin-CNPs suppressed the expression of pro-inflammatory cytokine and chemokine mRNA expression with increased wound healing efficacy, and tissue repair compared to the Octominin-alone-treated fish at 7 dpw. Together, the observed results give insights into the use of nanoencapsulation as a means of drug delivery, especially for small peptides. Full article

Regenerative endodontic procedures (REPs) are a promising treatment for immature teeth with pulpal necrosis. However, the outcomes remain unpredictable, partly due to scaffold limitations. Beta-glucan (BG), a bioactive polysaccharide with regenerative properties, may enhance scaffold performance. This study aimed to fabricate BG-coated polyvinylpyrrolidone/cellulose acetate (PVP/CA) electrospun scaffolds and evaluate their physicochemical properties and cell attachment. Electrospun scaffolds were fabricated by electrospinning a 10% w/v PVP/CA (70:30) solution in acetone and N,N-dimethylacetamide (2:1) (PC). BG (8% w/v in 1 M NaOH) was electrosprayed onto the scaffold at 0.1, 0.2, and 0.4 mL volumes, generating PC-BG01, PC-BG02, and PC-BG04, respectively. Scaffold characterization included SEM, FTIR, BG enzymatic assay, water absorbance, degradation, and cell adhesion assays. SEM images of the scaffolds exhibited smooth cylindrical fibers (547.3–585.9 nm diameter) with high porosity (42.37–49.91%). BG particles were confirmed by elemental analysis and BG enzymatic assay. At 28 days, the PC group showed significant fiber diameter and porosity reduction. BG particle degradation was observed at 14 and 28 days. Notably, BG-coated scaffolds significantly enhanced initial apical papilla cell adhesion at 1 and 24 h. These findings highlight the potential of BG-coated scaffolds as bioactive scaffolds for REPs. Full article

Background: Using natural substances for cancer therapy has attracted considerable interest due to their safety and reduced systemic toxicity. Nigella sativa (NS) oil, a traditional natural oil rich in bioactive compounds, possesses significant therapeutic potential. Brucine (BR), an alkaloid, exhibits potent cytotoxicity against various cancer cell lines; however, its poor selectivity and high systemic toxicity limit its clinical application. Objective: To overcome these challenges, this study aimed to enhance drug delivery and improve therapeutic efficacy. Method: A PEGylated nanoemulsion (NE) incorporating NS and BR was developed and characterized for particle size, size distribution, zeta potential, viscosity, and drug content. The in vitro release of BR was evaluated both with and without serum incubation. A quantitative amount of serum protein associated with the surface of the NE was estimated, and a hemolytic safety assay was carried out. Finally, an in vitro cytotoxicity study was conducted, and the in vivo anti-tumor effect of the developed PEGylated BR-loaded NE was evaluated and compared with its naked counterpart. Result: The developed PEGylated BR-loaded NE possessed favorable characteristics as a nanocarrier for parenteral administration, with a particle size of 188.5 nm, a zeta potential of −1.61, a viscosity of 3.4 cP, and 99% drug content uniformity. It released up to 60.4% of BR over 12 h, while only 18.4 µg/µmol of the total lipids were adsorbed on the surface of the formulation, compared with 54.5 µg/µmol for the naked counterpart. The PEGylated NE was safe, inducing less than 5% of hemolysis, and displayed substantial inhibition of MDA cell growth. Conclusions: The PEGylated NE achieved a significant reduction in tumor volume, suggesting that PEGylated NE may serve as a promising platform for enhancing anti-tumor activity. Full article

Cellular senescence, a state of stable cell cycle arrest accompanied by a complex senescence-associated secretory phenotype (SASP), is a fundamental biological process implicated as a key driver of lung aging and lung age-related diseases (LARDs). This review provides a comprehensive overview of the rapidly evolving field of senotyping based on cellular heterogeneity in lung development and aging in health and disease. It also delves into the molecular mechanisms driving senescence and SASP production, highlighting pathways such as p53/p21, p16^INK4a/RB, mTOR, and p38 MAPK as therapeutic targets. The involvement of various novel SASP proteins, such as GDP15, cytokines/chemokines, growth factors, and DNA damage response proteins. We further highlight the effectiveness of senotherapeutics in mitigating the detrimental effects of senescent cell (SnC) accumulation within the lungs. It also outlines two main therapeutic approaches: senolytics, which selectively trigger apoptosis in SnCs, and senomorphics (also known as senostatics), which mitigate the detrimental effects of the SASP without necessarily removing the senescent cells. Various classes of senolytic and senomorphic drugs are currently in clinical trials including natural products (e.g., quercetin, fisetin, resveratrol) and repurposed drugs (e.g., dasatinib, navitoclax, metformin, rapamycin) that has demonstrated therapeutic promise in improving tissue function, alleviating LARDs, and extending health span. We discuss the future of these strategies in lung research and further elaborate upon the usability of novel approaches including HSP90 inhibitors, senolytic CAR-T cells, Antibody drug conjugate and galactose-modified prodrugs in influencing the field of personalized medicine in future. Overall, this comprehensive review highlights the progress made so far and the challenges faced in the field of cellular senescence including SnC heterogeneity, states of senescence, senotyping, immunosenescence, drug delivery, target specificity, long-term safety, and the need for robust cell-based biomarkers. Future perspectives, such as advanced delivery systems, and combination therapies, are considered critical for translating the potential of senotherapeutics into effective clinical applications for age-related pulmonary diseases/conditions. Full article