Promoting networking among all local stakeholders in order to enable people with dementia to participate in society is one of the objectives of the National Dementia Strategy (NDS). Dementia Competence Centers are tasked with promoting this networking. Only isolated scientific findings have so far been available to assist in the implementation of this task. The aim of the study is to gain insight into the role of Dementia Competence Centers in regional and local dementia networking. In expert interviews, representatives of the Dementia Competence Centers were systematically questioned for the first time about their networking activities, and the data were evaluated using reflective thematic analysis. Based on a total of 21 interviews, the role of Dementia Competence Centers as pioneers for regional and local dementia networking was identified. As pioneers, Dementia Competence Centers identify opportunities for networking activities, remove obstacles to sustainable dementia networks and create links to further develop dementia-specific networking concepts. In their role as pioneers, it is the task of Dementia Competence Centers to strengthen the independence and sustainability of dementia networks. In addition, the Dementia Competence Centers connect the various political and care-related levels in order to further develop networking in the field of dementia with a view to promoting social inclusion for people with dementia. The scientific findings from Germany's various federal states can be used via the joint working group of the Dementia Competence Centers to systematically promote networking expertise in both the Dementia Competence Centers and the regional and local dementia networks.
Solid-liquid triboelectric nanogenerators (SL‑TENGs) have achieved notable progress in blue energy harvesting; however, their practical deployment is still limited by generally low and discontinuous current output. Here, we report a spray‑based TENG (S‑TENG) that introduces a dedicated spark discharge device (SDD) for active charge accumulation and controlled release. This design shifts the discharge process from the conventional passive and stochastic breakdown to an active, periodic spark‑discharge regime. Consequently, the S‑TENG delivers a breakthrough instantaneous short‑circuit current of 665 mA and an open‑circuit voltage of 900 V, operating continuously at 122 Hz, representing an improvement of over two orders of magnitude in both current amplitude and frequency compared to typical SL‑TENGs. Based on this high‑power output, the S‑TENG can directly illuminate a 110 W incandescent lamp or simultaneously drive 4000 commercial LEDs. When integrated with a power‑management circuit, it further enables water electrolysis for hydrogen production with an efficiency of 55.8%. This work not only pushes the current output of SL‑TENGs into the milliampere range but also provides a new strategy-through structural decoupling and active discharge regulation-to enhance the power density of TENGs, paving the way for their application in marine energy harvesting and electrochemical synthesis.
Estrogen operates as a pleiotropic steroidal, neuroendocrine modulator to combat accelerated brain ageing and neurodegeneration by addressing a convergent inflammatory-metabolic trio. Estrogen receptor-dependent neural cellular signalling reduces TLR4-mediated immune priming and NF-κB activation, preventing NLRP3 inflammasome assembly and pro-inflammatory cytokine release. Concurrently, estrogen increases SIRT1 activity, restoring metabolic and epigenetic equilibrium while inhibiting HMGB1 acetylation, translocation, extracellular release, and activation of the stress-response pathway. Coordinated regulation of the TLR4-NFκB-NLRP3 and SIRT1-HMGB1 molecular triad reduces chronic neuroinflammation, preserves neuronal integrity, metabolic resilience, and slows persistent inflammation-driven brain ageing. This highlights estrogen and estrogen-based steroidal modulators as promising therapeutic candidates for reversing accelerated cognitive ageing and neurodegenerative disorders. However, a crucial research gap persists in the absence of a systems-level assessment of neurosteroids as a multi-target regulator of convergent innate immunological and metabolic signalling networks. The control of the TLR4-NFκB-NLRP3 inflammasome axis and the SIRT1-HMGB1 metabolic-epigenetic checkpoint has not been well studied as an interrelated, steroidal druggable trifecta driving brain homeostasis and neurodegeneration. These pathways are often studied in isolation, despite overwhelming evidence that their bidirectional interplay contributes to persistent neuroinflammation, immunometabolic dysfunction, and cellular senescence. This review synthesises evidence from molecular endocrinology, biochemical, pre-clinical, and clinical models to advance a mechanistically integrated and therapeutically actionable framework that aligns into a unified endocrine, metabolic, and immune target-driven framework relevant to complex, inflammation-driven brain ageing, thereby offering a strong foundation and paving the way for future molecular target validation and disease-modifying, steroid-mimetic interventions against neurodegeneration.
Silver bismuth sulfide (AgBiS2) nanocrystals (NCs) have emerged as a premier eco-friendly and lead-free alternative for next-generation photovoltaics due to their exceptional light-harvesting capabilities. However, the efficiency of AgBiS2 solar cells is fundamentally constrained by detrimental band-tail states arising from internanocrystal heterogeneity and surface defects introduced during traditional ligand exchange. In this work, we demonstrate a strategy to flatten the energy landscape of AgBiS2 films by achieving macroscopic uniformity and long-range ordered self-assembly. By kinetically decoupling the reaction of Ag and Bi precursors, we produce highly monodisperse, directly conductive NC inks that bypass the need for efficiency-limiting ligand exchange processes. This approach ensures exceptional compositional homogeneity and suppresses nonradiative recombination, resulting in significantly enhanced carrier transport and extended lifetimes. Consequently, our eco-friendly AgBiS21 solar cells achieve a power conversion efficiency of 10.52%, representing one of the highest reported values for this class of nontoxic materials. This work provides a critical paradigm for mitigating energetic disorder in multinary semiconductors, paving the way for low-cost, high-performance, and environmentally benign thin-film photovoltaics.
The demand for off-the-shelf biocompatible bone substitutes has driven the development of numerous independent in vitro technologies to generate products resembling physiological tissues. Due to technical challenges and overly simplified cultivation approaches/niches, the end-products are often uniformly shaped and inferior to native bone tissue. In this report, three major technologies are implemented cohesively to address these shortfalls: (1) Spinner flasks for scaled-up stem cell expansion, (2) Manufacturing via 3D-printing and cast-molding processes, large modular collagen-based (COL) scaffolds +/- chondroitin sulfate A (CSA) of tailored dimensions, (3) Perfusion bioreactor with controlled oxygen tension (pO2) to support high cell density and osteochondral differentiation. We report an oxygenated in vitro niche within the bioreactor that supports high cell density and self-induced osteogenic differentiation for 60 days. Enhanced mineralization and osteogenic gene expression in COL scaffolds were observed, while COL + CSA scaffolds exhibited elevated Col10a gene expression for hypertrophic chondrocytes, a representative indicator of active endochondral ossification. In summary, this report describes an integral approach to consistently and rapidly achieve physiologically relevant bone substitutes of tailored dimensions. Furthermore, the pivotal effect of recapitulating endochondral ossification in vitro through dynamic bioreactor culture is demonstrated, paving the way to generate complex tissue structures in the future.
Optogenetics represents a promising frontier in precision cancer therapy by enabling spatiotemporal control over cellular behavior. However, its clinical application is limited by inefficient delivery of optogenetic components and poor tissue penetration of visible light. Recent advances in nanotechnology offer solutions to these challenges. Nanoscale drug delivery systems enhance the targeted delivery of optogenetic tools, while light-conversion nanomaterials enable deep-tissue activation. Besides, the integration of nanotechnology with optogenetics further facilitates the development of engineered living therapeutics, including immune cells and bacteria, allowing programmable and localized antitumor responses. Despite promising preclinical progress, key challenges remain in long-term biosafety, immunogenicity, and precise light dosing. Future progress will depend on interdisciplinary efforts combining biocompatible nanomaterials, protein engineering, and artificial intelligence to advance clinically viable optogenetic therapies and pave the way toward personalized cancer treatment. Collectively, the synergistic integration of optogenetics and nanotechnology holds potential for overcoming longstanding barriers in cancer treatment, paving the way for precision cancer therapeutics.
Therapeutic drug monitoring (TDM) for type 2 diabetes medications like metformin is challenging due to the lack of rapid and sensitive methods. Standard assays are often inaccurate, time-consuming, and fail to capture real-time pharmacokinetic (PK) fluctuations. Here, we developed a portable organic electrochemical transistor (OECT) sensing system for continuous, real-time tracking of metformin levels. The laser-engraved OECT biosensor is functionalized with a specific Fe2O3 nanozyme on the gate electrode for electrocatalytic oxidation of metformin, enabling highly sensitive and selective detection. Seamless integration with a smartphone application and OECT system provides dynamic real-time metformin PK monitoring in vitro, fostering a pharmacologically informed approach to diabetes management. Our findings confirm the system's potential for home-care precision PK monitoring, paving the way for personalized diabetes care.
Diabetic wounds remain a major clinical challenge owing to persistent dysregulation of the wound microenvironment, which substantially limits the effectiveness of conventional therapies. In recent years, multifunctional hydrogels have emerged as promising platforms for diabetic wound management, attributed to their excellent biocompatibility, tunable physicochemical properties, and unique capacity to actively remodel pathological microenvironments through integrated therapeutic functions. This comprehensive narrative review provides an in-depth synthesis of the pathogenesis and current therapeutic strategies for diabetic wounds, with a particular focus on recent advances in multifunctional hydrogels, as well as their classification, design principles, mechanisms of action, and translational potential. Furthermore, emerging directions are discussed as promising approaches for next-generation therapies, including intelligent closed-loop systems, interdisciplinary technological convergence, and the integration of bioactive components derived from traditional Chinese medicine. Collectively, these advances are poised to facilitate the transition from passive wound coverage to active microenvironment remodeling, paving the way for precision and personalized diabetic wound care.
Aqueous zinc-ion batteries (AZIBs) hold promise for sustainable energy storage, but high-capacity ammonium vanadate (NH4V4O10, NVO) cathodes suffer from sluggish Zn2+ kinetics and structural degradation via vanadium dissolution. To overcome these persistent bottlenecks, we propose a decoupled dual-modification strategy integrating the controlled partial substitution of interlayer NH4 + with hydronium ions (H3O+) and the in-situ formation of a conformal poly(3,4-ethylenedioxythiophene) (PEDOT) conductive network. Mechanistic and density functional theory (DFT) studies reveal that acid-induced proton exchange expands the interlayer spacing, significantly lowering the Zn2+ diffusion barrier. Conversely, the PEDOT coating acts as a "structural-electronic" bridge, compensating for the conductivity loss associated with deammoniation while serving as a robust physical barrier that suppresses the formation of the electrochemically inactive Zn3(OH)2V2O7·2H2O passivation layer. The resulting NVO@PEDOT cathode delivers an exceptional specific capacity of 360.2 mAh g-1, superior rate capability (110 mAh g-1 at an ultra-high current density of 30 A g-1), and remarkably robust cycling stability. It retains 94.0% of the capacity after 200 cycles at 0.5 A g-1 and 69.2% after 10 000 cycles at a high rate of 15 A g-1. This work establishes a versatile design strategy for decoupling kinetic and stability challenges in the cathode, paving the way for practical, high-rate AZIBs.
Developing cathode prelithiation technology to offset irreversible active lithium loss is essential for high-energy-density batteries. Antifluorite Li-rich Li5FeO4 (LFO) is a promising cathode prelithiation agent, owing to its high theoretical capacity and a suitable voltage window. However, industrial observation reveals that when LFO loading exceeds a critical threshold, graphite‖LiFePO4 (Gr‖LFP) pouch cells exhibit continuous gas evolution during storage and cycling, posing a latent safety hazard that hinders further application. Here, we systematically elucidate that the kinetic mismatch between LFO and LFP results in the incomplete decomposition of LFO, leaving residual reactive oxygen species that drive parasitic side reactions. Furthermore, we tailor the band structure and oxygen oxidation pathway of LFO via Mn doping to obtain LFMO, thereby enhancing electronic conductivity and stabilizing oxygen electron holes to accelerate decomposition kinetics. Consequently, the prelithiation capacity of LFMO increases to 752.5 mAh g-1 (a 7.8% improvement). Incorporating 2.7 wt% LFMO into pouch cells increases energy density by 2.4% and markedly suppresses gassing, paving the way for high-energy-density and inherently safe power batteries.
Erythrocyte-based drug delivery systems serve as an attractive strategy for cancer immunotherapy with improved biocompatibility, increased circulation time, and less immunogenicity. Due to their distinct physiological characteristics, erythrocytes can be developed as biomimetic carriers for targeted drug delivery, antigen presentation, and immune modulation. This review discusses the different strategies utilized to leverage erythrocytes in cancer immunotherapy, such as erythrocyte membrane-coated nanoparticles, antigen-hitchhiking systems, and immune-stimulatory erythrocyte-derived vesicles. Notably, we uniquely contextualizes erythrocyte-inspired platforms across each stage of the cancer-immunity cycle, highlighting their dual role as both drug delivery vehicles and active immunomodulators. We have explained how engineered erythrocyte-based systems enhance the cycle of cancer-immunity by increasing tumor antigen presentation and reshaping the tumor microenvironment for greater immune cell infiltration and cytotoxicity. In addition, recent advances in erythrocyte-based immunotherapeutic platforms, their advantages over conventional delivery platforms, and challenges in their clinical application are discussed. Overall, the integration of erythrocyte biomimetic technology into immunotherapy provides a novel approach to enhance cancer treatment efficacy and reduce systemic toxicity, paving the way for more targeted and effective therapies.
We introduce accelerated sequential posterior inference via reuse (ASPIRE), a broadly applicable framework that transforms existing posterior samples and Bayesian evidence estimates into unbiased results under alternative models without rerunning the original analysis. ASPIRE combines normalizing flows with a generalized sequential Monte Carlo (SMC) scheme, enabling efficient updates of existing results and reducing total likelihood evaluations and wall times by factors of up to 5.8 and 5.5, respectively, with larger gains per posterior sample. This addresses a growing problem in gravitational-wave astronomy, where events must be repeatedly reanalyzed under different models or physical hypotheses. We show that ASPIRE reproduces full Bayesian results when switching waveform models or adding physical effects such as spin precession and orbital eccentricity. With this statistical robustness, ASPIRE turns repeated reanalyses into fast, reliable updates-paving the way for systematic studies of waveform systematics, scalable reanalyses across large event catalogs, and broadly applicable Bayesian reanalysis across other scientific domains.
Benzothiadiazole derivatives (BTZ) have established themselves as benchmarks in nonlinear optical (NLO) research, owing to their exceptional charge-transfer capabilities and extensive electronic delocalization. With a unique blend of structural versatility and electronic tunability, these compounds hold immense potential for revolutionary modern optical applications. We developed a tailored set of BTZ derivatives, comprising four core-centered (C-1PhTDZ to C-2PhDTDZ) and four terminal-substituted (T-1PhTDZ to T-2PhDTDZ) compounds, by systematically modifying the acceptor unit size and placement to promote extended π-conjugation and enhance NLO responses. Overall, T-2PhDTDZ showed exceptional planarity (molecular planarity measurement; MPP 0.002 Å; span of deviation from plane, SDP 0.006 Å) due to enhanced intramolecular charge transfer (ICT) from terminal BTZ placement, boosting charge separation and performance. C-2PhDTDZ and T-2PhDTDZ exhibit the notable isotropic (αiso) and anisotropic (αaniso) polarizabilities, with values of 365.1 × 10-24 esu, 93.8 × 10-24 esu, 879.10 × 10-24 esu, and 113 × 10-24 esu, respectively. Within the terminal series, T-2PhDTDZ shows the highest total third-order NLO polarizability (<γ>) of 5128.8 × 10-36 esu, which is approximately 1.2 to 6.4 times larger than other derivatives. While among core series, C-1PhDTDZ exhibits a remarkably enhanced NLO response, attaining the maximum γ value of 1906.0 × 10-36 esu. Additionally, frequency-dependent γ was computed, with T-2PhDTDZ exhibiting the largest amplitudes for γ(-ω;ω,0,0) and γ(-2ω;ω,ω,0) at 1400 nm, with values of 247.90 × 10-36 esu and 324.53 × 10-36 esu, respectively. Moreover, the density of states (DOS) and natural bond orbital (NBO) analyses provide further insights into the electronic structure and charge transfer characteristics. We compared the Voc values of our designed derivatives with those of PC61BM. Notably, T-2PhDTDZ shows a pronounced offset value of 3.1 eV, which favors rapid electron injection and reduces energy loss. These findings suggest that our designed core-versus terminal-based BTZ derivatives possess significant advancements in NLO and photovoltaic technologies, paving the way for next-generation optoelectronics and photonic applications.
Synchronization resulting in unified collective behavior of the individual elements of a system that are weakly coupled to each other has long fascinated scientists. Examples range from the periodic oscillation of coupled pendulum clocks to the rhythmic behavior in biological systems. Here we demonstrate this effect in a solid-state platform: spatially remote, auto-oscillating electron-nuclear spin systems in a semiconductor. When two such oscillators separated by up to 40 μm are optically pumped, their individually different frequencies lock to a common value, revealing long-range coupling. For larger separations, the synchronization breaks. The interaction distance matches the electron spin diffusion length, identifying spin transport as the coupling-mediating mechanism and maintaining correlated behavior over mesoscopic distances. As a consequence, a wide-area optical pump drives all oscillators within the illuminated spot into a single synchronized state, despite their inhomogeneity. This synchronization accounts for the exceptional stability of the resulting auto-oscillations, enabling collective motion in distributed spin systems and paving the way toward spin networks in spintronics.
Ischemic heart disease is the main cause of death in developed countries, and full recovery remains unachievable. A potential cure can be based on utilizing miRNAs capable of triggering cardiac regeneration by stimulating cardiomyocyte proliferation. However, to deliver miRNAs efficiently, nanocarriers are required for protection from rapid cleavage in the extracellular milieu and successful uptake by cardiomyocytes. Here, we present biocompatible chitosan nanoparticles, formulated via a green polyelectrolyte complexation process, and efficiently loaded with miR199a-3p. Their safety and therapeutic potential were evaluated in vitro and in vivo. To enhance cardiac accumulation, we further explored the functionalization of these nanoparticles with tannic acid, a polyphenolic compound that exhibits favored cardiac targeting and sustained retention. Thus, we have optimized the miR-loaded chitosan-based formulation to achieve tunable sizes (100-300 nm) while maintaining high biocompatibility with HL-1 cardiomyocytes and primary murine or rat cardiomyocytes. Notably, miRNA-loaded nanoparticles boosted cardiomyocyte proliferation by up to 75%. Confocal microscopy confirmed successful uptake by cardiomyocytes. In vivo, no mortality or adverse effects were observed during the 4-day observation period, with miRNA expression increasing up to sixfold and target gene downregulation reaching 50%. These findings establish a proof of concept that chitosan-based polyelectrolyte complexes can serve as a safe and effective nanoplatform for delivering regenerative miRNAs to the heart, paving the way for next-generation cardiac therapies.
Tumor-associated microbes like Fusobacterium nucleatum (F. nucleatum) critically contribute to immunosuppression and hinder cancer therapy. To overcome this challenge, we developed a microbe-targeted immune reprogramming strategy utilizing tumor cell membrane-camouflaged Ag@MSN-PpIX nanoparticles (M-MAP). Under ultrasound irradiation, M-MAP specifically eliminates intratumoral F. nucleatum, thereby directly reversing F. nucleatum-mediated immunosuppression while preserving gut microbiota homeostasis. Crucially, the killed F. nucleatum acts as an immunostimulant, promoting robust activation of antigen-presenting cells (APCs) and enhancing infiltration of cytotoxic T lymphocytes (CTLs) within the tumor. This dual action-elimination of suppressive bacteria and immunogenic activation by bacterial remnants-effectively reprograms the immunosuppressive tumor microenvironment (TME) in colorectal cancer. This work proposes a therapeutic strategy for cancer that targets tumor-associated bacteria to reprogram the TME, paving the way for more effective cancer treatments.
FLASH radiotherapy delivers ultra-high dose rate radiation (>40 Gy/s) has shown promise in reducing normal tissue toxicity while maintaining tumor control. IBA's single-room proton system, equipped with S2C2 superconducting synchrocyclotron accelerator, has recently demonstrated to achieve UHDR delivery. Integrating the UHDR beam line in the treatment planning system (TPS) is crucial for accurate dose calculation in preclinical study, optimization of the 2D dose profile as well as paving the way for further accessory development for spread-out Bragg peak FLASH. This study aims to commission and validate a synchrocyclotron-based pencil beam scanning UHDR proton beamline on the IBA ProteusONE system in RayStation TPS. The goal is to establish a framework for TPS modeling and validation, facilitating preclinical FLASH radiotherapy studies. The transmission UHDR beamline using scanning proton beam energy of 228 MeV was characterized at gantry 0° using comprehensive point dose and 2D lateral profiles measurements. The beam model was developed in RayStation, incorporating key parameters such as virtual source position, spot size, integrated depth dose (IDD), and absolute dose calibration. Extensive validations were conducted using ionization chambers, film dosimetry, and 2D scintillation detectors, with gamma analysis performed to assess the accuracy of the TPS model with open field and field in the presence of brass apertures. The UHDR beamline achieved ultra-high dose rates exceeding 40 Gy/s (average dose rate for a 2.5 x 2.5 cm field) with consistent dose output validated across multiple detectors. The nozzle current was measured to be linear with respect to the requested MU in the range of 45 to 126 nA. The RayStation beam model demonstrated excellent agreement with experimental measurements, achieving less than 2.5% deviation for all point dose measurements. For 2D profile measurements, gamma passing rates >95% under 2%/2 mm criteria for all fields. The TPS allowed optimization of the spot pattern for UHDR FLASH beams aligned closely with clinical beam profiles, enabling accurate preclinical study comparisons. A synchrocyclotron-based UHDR beamline was successfully commissioned and validated through a reliable TPS model for transmission FLASH application. The results provide a foundation for preclinical FLASH-RT research and future clinical applications, demonstrating the feasibility of integrating FLASH-RT into existing proton therapy platforms. Future work will extend the commissioning to all gantry angles and explore spread-out Bragg peak FLASH delivery for improved dose conformality.
Spin-crossover (SCO) nanoparticles (NPs) of the ID coordination polymer [Fe-(HTrz)2(Trz)]·(BF4), where HTrz = 1H-1,2,4-triazole, have been synthesized with integrated luminescence properties, focusing on the role of dopant trivalent Terbium (Tb) ions. Using a reverse micelle method, three types of nanoparticles were synthesized: pristine NPs (NP1), silica covered (NP2), and Tb-doped (NP3) NPs. Structural and morphological analyses, including TEM, STEM-XEDS, FT-IR, P-XRD, XPS, and XAFS spectroscopy, confirmed the successful incorporation of Tb ions into the silica matrix of NP3 and revealed their bonding environment with SiO4 tetrahedra and nitrate ions. Magnetic susceptibility measurements demonstrated hysteretic SCO behavior in all nanoparticle types, with NP3 exhibiting the highest thermal hysteresis width and a shift in critical temperatures, indicating enhanced cooperativity and modified magnetic properties due to the presence of Tb ions. Temperature-dependent photoluminescence (PL) measurements of NP3 showed hysteresis during thermal cycling, attributed to SCO transitions between high- and low-spin states. The study highlights the synergy between SCO and luminescence properties, paving the way for the development of multifunctional materials for applications in optoelectronics, sensors, and thermometry. These findings provide valuable insights into the design and optimization of advanced SCO-luminescent nanomaterials.
Clear cell renal cell carcinoma (ccRCC) is a prevalent malignancy, representing 80-90% of kidney cancer cases. This study aimed to identify potential prognostic genes to improve patient survival prediction and provide new insights into the pathogenesis and treatment of ccRCC through comprehensive whole transcriptome sequencing analysis. The analysis utilized whole transcriptomic data from publicly available datasets, including TCGA-KIRC and GSE96574. Methods involved identifying differentially expressed mRNAs and long non-coding RNAs, prognostic gene screening via MCODE plugin and risk model construction, followed by functional enrichment, molecular network construction, drug prediction, and molecular docking. The expression levels of key genes were subsequently validated using reverse transcription quantitative PCR (RT-qPCR) on clinical samples. Eight prognostic genes (IFNG, CXCL13, KLRK1, LAG3, ITGAX, TNFRSF9, CD2, CD8B) were identified and formed a risk stratification model. These genes were primarily enriched in immune-related pathways such as antigen processing and presentation. A regulatory network involving transcription factors, miRNAs, lncRNA PVT1, and circRNAs was constructed. Drug prediction and molecular docking suggested potential targeted drugs, including amitriptyline hydrochloride for CD8B and IFNG, and rituximab for CXCL13 and IFNG, with strong binding affinities noted for ITGAX and KLRK1. RT-qPCR validation confirmed significantly elevated expression of IFNG, LAG3, TNFRSF9, and CD8B in ccRCC patients compared to controls (p < 0.05). This study identifies an eight-gene signature as a promising prognostic biomarker for ccRCC, deeply involved in the tumor immune microenvironment. The findings offer novel insights into ccRCC pathogenesis and highlight potential therapeutic targets and agents, paving the way for improved prognostic strategies and immunotherapeutic approaches.
The study explores sodium alginate nanogels encapsulating cholecalciferol (vitamin D3) as a novel topical therapeutic for skin cancer, targeting LOX IMVI (melanoma) and A431 (epidermoid carcinoma) cell lines. Nanogels were prepared using magnetic stirring and sonication, resulting in a uniform dispersion and enhanced stability. Physicochemical characterization revealed a particle size of 67.6 ± 13.43 nm, a polydispersity index (PDI) of 0.30 ± 0.02, and a ζ-potential of -25.00 ± 2.00 mV, confirming good colloidal stability and suitability for topical application. In vitro drug release studies demonstrated a sustained-release profile, with 89.73 ± 2.1% cholecalciferol released over 34 h, as predicted by a first-order kinetic model (R 2 = 0.9871). Cytotoxicity assays showed significant anticancer activity, with IC50 values of 29.51 ± 1.56 and 24.95 ± 1.32 μM for LOX IMVI and A431 cell lines, respectively, while exhibiting reduced cytotoxicity against normal HSF cells (IC50 = 83.88 ± 4.43 μM). Cell-cycle analysis indicated G1/S phase arrest, and Annexin V-FITC/PI staining confirmed apoptosis induction with minimal necrosis. Molecular docking studies validated the mechanism of action, revealing strong binding of cholecalciferol to the vitamin D receptor (VDR) through hydrogen bonding with SER278 and SER275, π-cation interaction with TRP286, and hydrophobic interactions, with a docking score of -11.7 kcal/mol. These findings suggest sodium alginate nanogels encapsulating cholecalciferol as a promising, biocompatible therapeutic for the topical treatment of skin cancer, paving the way for future clinical investigations.