Search Results (2,438)

Orthodontic tooth movement (OTM) is accompanied by sterile inflammation, a necessary biological process that facilitates tooth displacement but also contributes to adverse effects, including hyalinization and orthodontically induced external apical root resorption (OEARR). Despite advancements in orthodontic therapies, the inflammatory response—regulated by dynamic interactions between tissue-specific cells and their molecular mediators—remains a critical factor influencing treatment outcomes. This review summarizes the current understanding of the cellular and molecular mechanisms underlying OTM, with a focus on how these insights can support the development of targeted therapeutic strategies. These include cell- and molecule-based therapies, biomaterial-mediated delivery systems, and applications of artificial intelligence (AI). Notably, AI offers promising opportunities for modeling and simulating biological responses, enabling the optimization of individualized treatment planning. We further discuss current clinical practices and highlight emerging experimental findings, with an emphasis on unresolved research questions pivotal to improving therapeutic efficacy and reducing complications such as OEARR. This comprehensive overview aims to inform future directions in orthodontics by integrating mechanistic knowledge with technological innovation. Full article

Molecularly imprinted polymer nanoparticles (MIP NPs) are synthetic receptors with selective recognition sites for target molecules. They are employed instead of biorecognition elements in many applications due to their high affinity and selectivity, stability, easy preparation, and low cost. Their nanoscale size provides enhanced surface interactions, faster response times, improved biocompatibility, and effective cellular penetration, particularly in complex biological environments. MIP NPs provide high selectivity and structural versatility in the sample preparation, sensor-based detection, and controlled drug delivery, serving as promising alternatives to conventional methods. This review highlights the recent advancements in the synthesis and application of MIP NPs in three critical areas: sample preparation, sensor-based detection, and controlled drug release. Additionally, recent developments in green synthesis approaches, biocompatible materials, and surface functionalization strategies that are effective in the performance of MIP NPs are mentioned. Full article

Survivin, a pivotal member of the inhibitor of apoptosis proteins (IAP) family, plays critical roles in cell cycle regulation and division. Survivin is overexpressed in most malignancies, making it an attractive therapeutic target. Due to its high specificity and potency, siRNA-based RNA interference (RNAi) has emerged as a powerful therapeutic strategy for effectively downregulating disease-related genes such as survivin in cancer therapy. However, naked siRNA suffers from rapid enzymatic degradation, poor cellular uptake, and off-target effects, severely limiting its therapeutic efficacy in vivo. Development of polymer-based nanocarriers for tumor-targeted delivery of survivin siRNA (siSurvivin) holds great potential to address these challenges. In this review, we first described the structure and function of survivin and summarized the survivin-targeted therapeutic strategy. Then, the siRNA delivery systems, particularly the polymeric nanocarriers, were introduced. Furthermore, a plethora of polymer-based nanocarriers for tumor-targeted siSurvivin delivery, including synthetic polymers (branched polymers, dendritic polymers, polymeric micelles), natural polymers (polysaccharides, proteins, and others), lipid-polymer hybrid nanoparticles, and polymer composite nanoparticles, were elaborated. Promising results underscore the potential of polymer-based nanocarriers for survivin siRNA delivery to enhance cancer therapy, providing a roadmap for future clinical translation. Full article

MRNA-based therapeutics and vaccines represent a rapidly expanding frontier in biomedical innovation, with lipid nanoparticles (LNPs) serving as a clinically validated delivery platform. This study explores critical quality attributes of LNP-mRNA formulations, with a particular focus on in vitro biological activity, a key quality attribute of vaccine activity and batch-to-batch consistency. We discuss the importance of optimizing both LNP components and mRNA structure, highlighting recent advances in formulation strategies. Furthermore, we examine the influence of factors such as cell-line selection, experimental design, storage conditions, and targeted cellular delivery on transduction efficiency. Our findings underscore the need for standardized in vitro assays and process-integrated monitoring to support the scalable development and regulatory assessment of mRNA-based therapies. Full article

Lung cancer remains a foremost cause of cancer-related impermanence globally, demanding innovative and effective therapeutic strategies. Polymeric nanoparticles (NPs) have turned up as a promising transport system for drugs due to their biodegradability, biocompatibility, and capability to provide controlled and targeted release of therapeutic agents. This review offers a thorough examination of different polymeric NP platforms, such as chitosan, gelatin, alginate, poly (lactic acid), and polycaprolactone, highlighting their mechanisms, formulations, and applications in the treatment of lung cancer. These NPs facilitate the delivery of chemotherapeutic agents, gene therapies, and immune modulators, with enhanced bioavailability and reduced systemic toxicity. Additionally, advanced formulations such as ligand-conjugated, stimuli-responsive, and multifunctional NPs demonstrate improved tumor-specific accumulation and cellular uptake. The review also discusses quantum dots, magnetic and lipid-based NPs, and green-synthesized metallic polymeric hybrids, emphasizing their potential in theranostics and combination therapies. Preclinical studies show promising results, yet clinical translation faces challenges; for example, large-scale production, long-term toxicity, and regulatory hurdles. Overall, polymeric NPs represent a powerful platform for advancing personalized lung cancer therapy, with future prospects rooted in multifunctional, targeted, and patient-specific nanomedicine. Full article

Significant progress has been made in developing cell-based drug delivery systems that utilize the intrinsic biological properties of various cell types—erythrocytes, leukocytes, platelets, stem cells, and even spermatozoa—to improve drug targeting, bioavailability, and biocompatibility. This review presents an integrative analysis of the latest advances in cell-based drug delivery systems, focusing on their design, pharmacokinetics, cellular interactions, and therapeutic potential. We specifically focus on hybrid microrobots and membrane-coated nanocarriers as emerging biohybrid platforms. Despite these advances, translation to the clinical phase remains constrained by persistent limitations, such as immune clearance, loss of membrane integrity during cargo loading, limited tissue penetration of carrier cells, and manufacturing challenges. Finally, we highlight future directions, including CAR-cell combinations and artificial cell engineering, that promise to expand the clinical utility of cell-based drug delivery systems in oncology, infectious diseases, and regenerative medicine. Full article

Background and Objectives: Acute normovolemic hemodilution (ANH) is commonly used to minimize perioperative blood loss and transfusion requirements. While it is considered safe, the molecular effects of ANH on vital organs remain unclear. Aquaporins (AQPs), the principal cellular water transporters, may play a role in tissue adaptation or injury under hemodilution stress. This study aimed to evaluate the impact of ANH on AQP1, AQP3, and AQP4 expression profiles and their association with apoptotic and inflammatory markers in the aorta, heart, kidney, and liver. Materials and Methods: Male Hannover–Sprague Dawley rats (6 months old) were assigned to control (no procedure), sham (anesthesia only), and hemodilution (anesthesia and ANH) groups. ANH was induced using balanced crystalloid infusion. Physiological parameters, blood gases, electrolytes, and metabolic profiles were monitored. At 24 h post-ANH, tissues were harvested for immunoblot analysis of AQPs, as well as apoptotic and inflammatory markers. Results: At 24 h post-ANH, changes in potassium, calcium, and glucose levels, decreased hematocrit, increased lactate, decreased pH, base excess, and PaCO₂ were detected, indicating mild metabolic acidosis due to tissue hypoxia and impaired oxygen delivery. Apoptotic and inflammatory responses were observed across all tissues, but AQP alterations were organ-specific. In the heart, AQP1 downregulation correlated inversely with NF-κB and TNF-α levels, while AQP3 upregulation positively correlated with apoptosis. The aorta showed the opposite pattern. In the kidney, AQP4 downregulation was strongly associated with apoptosis and inflammation. Furthermore, ANH selectively increased the AQP3 expression without affecting AQP1 or AQP4 in the liver. Conclusion: ANH induces differential aquaporin expression patterns in major organs, with tissue-specific associations with apoptosis and inflammation. These findings highlight a potential mechanistic role for AQPs, particularly AQP1 and AQP3, in modulating tissue response to hemodilution. These molecular adaptations may serve as early indicators of tissue stress, suggesting clinical relevance for perioperative fluid strategies. Full article

Stimuli-responsive, cell-mediated drug delivery systems represent a dynamic interface between biological functionality and engineered control. Leveraging the inherent targeting properties of erythrocytes, immune cells, stem cells, and exosomes, these systems offer a promising strategy for precise therapeutic delivery. In this review, we provide a comprehensive analysis of the design principles and biological underpinnings of stimuli-responsive carriers that release payloads in response to endogenous triggers (e.g., pH, redox, enzymatic activity) or external stimuli (e.g., light, ultrasound, magnetic fields). We further examine current strategies for loading and functionalizing cellular carriers, highlight key therapeutic applications across oncology and regenerative medicine, and assess translational progress and regulatory challenges. This review underscores the emerging clinical potential of intelligent cell-based delivery vehicles and outlines future directions for their optimization and implementation. Full article

Phytochemicals exhibit a broad spectrum of pharmacological activities, including significant anticancer potential. However, their clinical translation is often hampered by poor aqueous solubility, low bioavailability, and chemical instability. Lipid-based nanocarriers, especially solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have proven to be effective strategies for addressing these challenges. These nanocarriers improve the solubility, stability, and bioavailability of phytochemical-based anticancer agents, while enabling controlled and tumor-specific drug release. Encapsulation of anticancer phytochemicals such as curcumin, quercetin, resveratrol, silymarin, and naringenin in SLNs and NLCs has demonstrated improved therapeutic efficacy, cellular uptake, and reduced systemic toxicity. Co-delivery strategies, combining multiple phytochemicals or phytochemical–synthetic drug pairs, further contribute to synergistic anticancer effects, dose reduction, and minimized side effects, particularly important in complex cancers such as glioblastoma, breast, and colon cancers. This review presents a comparative overview of SLNs and NLCs in terms of formulation methods, in vitro characterization, and classification of key phytochemicals based on chemical structure and botanical sources. The roles of these lipidic carriers in enhancing anticancer activity, challenges in formulation, and recent patent filings are discussed to highlight ongoing innovations. Additionally, hybrid lipid–polymer nanoparticles are introduced as next-generation carriers combining the benefits of both systems. Future research should aim to develop scalable, biomimetic, and stimuli-responsive nanostructures through advanced surface engineering. Collaborative interdisciplinary efforts and regulatory harmonization are essential to translate these lipid-based carriers into clinically viable platforms for anticancer phytochemical delivery. Full article

Polymers and polymer composites offer versatile possibilities for engineering the physico-chemical properties of materials on micro- and macroscopic scales. This review provides an overview of polymeric and polymer-decorated particles that can serve as drug-delivery vectors: linear polymers, star polymers, diblock-copolymer micelles, polymer-grafted nanoparticles, polymersomes, stealth liposomes, microgels, and biomolecular condensates. The physico-chemical interactions between the delivery vectors and biological cells range from chemical interactions on the molecular scale to deformation energies on the particle scale. The focus of this review is on the structure and elastic properties of these particles, as well as their circulation in blood and cellular uptake. Furthermore, the effects of polymer decoration in vivo (e.g., of glycosylated plasma membranes, cortical cytoskeletal networks, and naturally occurring condensates) on drug delivery are discussed. Full article

Central nervous system (CNS) tumors, especially gliomas and IDH-wildtype glioblastoma, present high aggressiveness, low response to current treatments and limited survival. Several biological processes such as oxidative stress, inflammation, apoptosis, and autophagy are involved in their development. Hydroxytyrosol (HTX), a phenolic compound present in olives, has shown relevant effects on these processes in experimental models. This review analyzes its chemical characteristics, bioavailability, and ability to cross the blood–brain barrier, as well as its mechanisms of action. Despite its rapid metabolism, HTX can reach the brain in small but functional amounts, and various formulation methods can enhance its delivery to nervous tissue. HTX acts on cellular pathways such as Nrf2, NF-κB, JAK/STAT, PI3K/Akt and SIRT1, regulating redox balance, inflammation, programmed cell death, and autophagy. It can also influence gene expression through epigenetic mechanisms. In cell models, it has shown inhibitory effects on tumor growth and activation of apoptosis, without affecting non-tumor cells. These results support its possible usefulness as an adjunct in the treatment of brain tumors, although further studies in animal and human models are required. Full article

In recent years, combination chemotherapy with therapeutic nucleic acids has emerged as a promising strategy to enhance the effectiveness of cancer therapy. However, developing an effective co-delivery system to simultaneously transport both chemotherapeutic drugs and nucleic acids remains challenging. Herein, we fabricated cholesterol-conjugated polyion complex nanoparticles (PCNs) for combination delivery of hydrophobic paclitaxel (PTX) and hydrophilic miR-34a. Cholesterol was conjugated to polyethylenimine (PEI) and hyaluronic acid (HA), producing C–PEI and C–HA, respectively. PTX was initially encapsulated within the hydrophobic core formed by the self-assembly of C–HA and C–PEI, yielding polyion complex nanoparticles (PTX@C–HA/C–PEI PCNs). Subsequently, the negatively charged miR-34a was electrostatically complexed with the cationic C–PEI moieties to generate miR-34a/PTX@C–HA/C–PEI PCNs. These PCNs exhibited a nanoscale structure with a uniform size distribution and demonstrated low cytotoxicity in colon cancer cells. Fluorescence microscopy confirmed efficient cytosolic delivery of C–HA/C–PEI PCNs in colon carcinoma cells. Furthermore, combination delivery of PTX and miR-34a using C–HA/C–PEI PCNs exhibited significantly enhanced transfection efficiency and cellular uptake for human colon cancer cells. Notably, PTX/miR-34a@C–HA/C–PEI PCNs effectively downregulated critical oncogenic targets, including Notch1, Snail1, and BCL-2, resulting in reduced cancer cell migration and proliferation. These findings indicate that PTX/miR-34a@C–HA/C–PEI PCNs hold significant potential as an innovative combination delivery platform, offering improved therapeutic efficacy for colon cancer therapy. Full article

Tailored mesoporous silicate nanomaterials have attracted significant interest due to their exceptional surface properties, including high interfacial toughness, tunable thickness, customizable topology, optical transparency, and adjustable hydrophobicity. These characteristics enable them to exhibit a wide range of functional behaviors, such as antibacterial, anti-fouling, anti-fogging, lubricating, and abrasion-resistant properties, to name just a few. With recent advances in surface-modified nanosystems for bioengineering and biomedical applications, silica-based nanomaterials have emerged as promising candidates owing to their ease of surface functionalization, bioactivity, biocompatibility, biodegradability, and bioavailability. Consequently, they have been widely explored in various therapeutic contexts. This review provides a concise and concentrated summary of recent advances and applications of tailored mesoporous silicate nanomaterials in regenerative medicine and theranostics, with the primary focus being on how endogenous or exogenous triggers can be leveraged to achieve selective and precise delivery of various biomolecules and active therapeutics across diverse cellular environments, by harnessing the intrinsic properties of mesoporous silicate nanoparticles. This focus also guided the selection of specific examples provided to highlight their wide range of applications, with the report concluding with some perspectives and remaining challenges. Full article

Hederagenin, a pentacyclic triterpenoid saponin from various medicinal plants, shows immense therapeutic potential; however, its inherent low bioavailability severely hinders its clinical translation. This comprehensive review synthesizes recent studies on the health benefits of hederagenin and its glycosides, critically the chemical modification strategies and pharmacological mechanisms aimed at optimizing its bioactivity. Key findings reveal that its broad anticancer and anti-inflammatory activities largely stem from its capacity to modulate crucial cellular signaling pathways, including the NF-κB, PI3K/Akt, and MAPK. Structural modification, particularly intelligent derivatization at the C-28 position, is a central strategy to overcome its pharmacokinetic deficiencies and significantly boost cytotoxicity. Furthermore, its unique pro-oxidant function within cancer cells, achieved by inhibiting the Nrf2-ARE antioxidant pathway, offers a novel approach for selective chemotherapeutics. For the clinical translation of hederagenin, we propose a strategic focus on derivatization through multi-target hybrids and sophisticated delivery systems. This approach is essential for addressing its pharmacokinetic barriers while strategically leveraging its context-dependent pro-oxidant effects. Full article

Skin aging is commonly characterized by increased wrinkles, loss of elasticity, and hyperpigmentation, significantly affecting personal appearance and quality of life. Although botulinum toxin type A (BTX-A) has been widely applied in cosmetic anti-wrinkle treatments, its intrinsic cytotoxicity limits broader clinical applications. In this study, we developed a novel exosome-based BTX-A composite delivery system designed to synergize the anti-aging properties of exosomes with the wrinkle-reducing effects of BTX-A while reducing toxicity. Human adipose-derived mesenchymal stem cells were genetically modified via lentiviral transduction to overexpress Synaptic Vesicle Glycoprotein 2C (SV2C), the receptor of BTX-A, thereby producing SV2C-enriched functionalized exosomes (EXO^SV2C). These exosomes (2.0 × 10⁷ particles/mL) were incubated with BTX-A (3 U/mL) to generate the EXO^SV2C-BTX-A complex. In vitro, EXO^SV2C-BTX-A significantly promoted the proliferation and migration of human dermal fibroblasts and effectively alleviated D-galactose (D-gal)-induced cellular senescence and collagen type I loss. These effects were superior to those observed with either BTX-A or exosomes alone. In vivo, intradermal injection of EXO^SV2C-BTX-A for 28 days markedly suppressed D-gal-induced skin aging in 8-week-old male KM mice, as evidenced by reduced malondialdehyde levels in dermal tissue, enhanced collagen type I expression, and preserved skin structure. Notably, the composite exhibited significantly lower toxicity compared to free BTX-A. Collectively, these findings highlight EXO^SV2C-BTX-A as a promising exosome-mediated BTX-A delivery platform with enhanced anti-aging efficacy and improved biocompatibility, offering a potential therapeutic strategy for skin rejuvenation. Full article