Glioblastoma multiforme is a universally fatal brain tumor characterized by aggressive progression, therapeutic resistance, and inevitable recurrence. While direct neuron-glioblastoma structural connectivity is hypothesized to drive post-therapy resilience, isolating physical contact from soluble paracrine signaling in in vitro models has been limited by transport-related confounders. Here, we present a platform to effectively decouple these mechanisms by selectively regulating neurite-mediated contact via surface-functionalized Transwell pores, effectively decoupling structural connectivity from diffusion dynamics. Using this system, we demonstrated directional neurite penetration, alongside the formation of synapse-like structures and tumor microtube-associated interactions at the neuron-glioblastoma interface. Notably, following treatment with standard-of-care temozolomide, glioblastoma spheroids exhibited significantly accelerated regrowth exclusively when direct neurite contact was permitted. These results revealed that physical neural connectivity, distinct from paracrine signaling, acts as a critical mediator of post-chemotherapy recurrence. Our platform provides a rigorous, mechanistically interpretable method to quantify contact-dependent neural contributions to tumor biology, serving as a powerful tool for investigating neural drivers of glioblastoma and evaluating targeted interventions at the neuron-glioblastoma interface.
The sensitivity of biological imaging can be significantly enhanced by near-infrared (NIR) fluorescent dyes, which offer deep tissue penetration and low background interference. However, their practical application in targeted imaging is limited by low fluorescence intensity at the sites of interest, primarily caused by restricted availability of cellular binding sites and the hydrophobic nature of most NIR dyes, leading to compromised solubility and stability in aqueous milieus. To address these challenges, we design and synthesize a series of functional fluorescent polymers using poly(pentafluorophenyl acrylate) (PPFPA) as a versatile precursor for targeted modifications. The synthesis involves the conjugation of amine-functionalized IR775 NIR dye to the reactive PFP ester units, followed by the incorporation of poly(ethylene glycol) (PEG) chains to enhance hydrophilicity and biocompatibility. By tuning the dye-to-PEG ratio, the fluorescence intensity and self-assembly behavior of the polymers are modulated, yielding spherical nanoparticles with enhanced brightness at a dye loading of 25%. Biotinylation of the fluorescent copolymers then enables their targeted binding to biotin-receptor-containing surfaces. Enhancement in fluorescence signal detection postcellular internalization is demonstrated by in vitro imaging, and an increase in tissue penetration depth is shown by employing a tissue-like phantom model, validating the use of the developed fluorescent polymers as NIR probes for advanced imaging and diagnostic applications.
Wide-bandgap metal-oxide nanoparticles are promising candidates for broad-spectrum sunscreens, yet their application is limited by photocatalytic activity and insufficient high-energy visible (HEV) light absorption. Here, we report a simple, scalable one-pot strategy for the spontaneous formation of a metal-phenolic network (MPN) on zinc oxide (ZnO) nanoparticles (ZnO/MPN NPs), utilizing intrinsic Zn2+ ion release from ZnO to initiate tannic acid (TA) complexation and in situ oxidation. This process forms a nanoscale MPN layer on the ZnO surface, while ZnO-mediated TA oxidation and dimerization (inspired by natural fruit browning) enhance electron delocalization, extending light absorption to the HEV region. The resulting browned MPN-coated ZnO nanoparticles (ZnO/MPN-B NPs) exhibited approximately a threefold enhancement in both sun protection factor (SPF) and UVA protection factor (UVAPF) compared to uncoated ZnO NPs. Additionally, the MPN layer effectively suppresses over 99 % of photogenerated reactive oxygen species (ROS) through its intrinsic ROS scavenging properties, significantly improving photostability. Cell viability assays further demonstrate that the MPN layer mitigates photoinduced cytotoxicity, supporting the safety and biocompatibility of these hybrids. This study suggests ZnO/MPN-B NPs as eco-friendly, high-performance candidates for next-generation sunscreen formulations, offering a scalable, efficient route to address the dual challenges of photoprotection and safety in inorganic sunscreen agents.
Metal‐phenolic networks (MPNs) integrated with functionalized cellulose nanofibers present a promising platform for stabilizing oxidation‐sensitive compounds. Here, a novel antioxidant pickering emulsion system utilizing MPN‐decorated carboxyl‐functionalized pulp cellulose nanofibers (MPN‐PCNF) is demonstrated. The system exhibits exceptional interfacial stability through synergistic effects of MPN coating and alkyl functionalization, validated by DLVO theoretical modeling and rheological characterization. MPN‐PCNF demonstrates remarkable antioxidant efficacy, achieving 94% α‐tocopherol retention over 50 days and 80% reduction in cellular reactive oxygen species. In reconstructed human skin models, the system significantly attenuates UV‐induced oxidative stress, evidenced by preserved stratum corneum integrity and suppressed matrix metalloproteinase‐1 expression. This biocompatible platform represents a versatile solution for protecting oxidation‐sensitive compounds across pharmaceutical, cosmetic, and food applications, offering a sustainable alternative to conventional synthetic antioxidant systems.
Pressure injuries have garnered considerable attention in healthcare, particularly in individuals with limited mobility. Current pressure‐monitoring methods primarily analyze only physical signals, which are insufficient for accurately assessing patient status. Biofluids contain rich chemical information that can reveal new insights for the comprehensive monitoring of pressure‐derived tissue damage and ulcer formation. However, challenges related to multimodal sensing capabilities and lack of all‐in‐one analytical tools hinder practical applications in clinical settings. This paper introduces a battery‐free, wireless multi‐sensing device for real‐time, in situ monitoring of the mechanical and chemical aspects of pressure injury and hygiene management. The device includes an optoelectronic pressure sensor (≈10 kPa), a temperature sensor (≈40 °C), a highly selective NH 3 gas sensor (ppm level) that operates at room temperature and has antibacterial properties, and near‐field communication reading circuits. The capability of the device for simultaneous and continuous monitoring of mechanical and chemical conditions in pressure‐localized areas without mutual signal interference has been validated. Furthermore, the usability and multimodal sensing capability of the device are validated through human subject studies involving diverse physical conditions, demonstrating its feasibility and robustness in real‐world clinical environments.
Photodetectors are essential for imaging, optical communication, and chemical sensing due to their ability to convert optical signals into electrical outputs. Metal halide perovskites (MHPs) with their excellent optoelectronic properties are promising materials for developing high-performance photodetectors. However, conventional SnOx deposition via sputtering in photodetector device architectures can damage underlying interfacial layers (e.g., C60), reducing the device performance. To overcome this, we developed a low-temperature atomic layer deposition (ALD) process for SnOx, coupled with a hybrid interfacial layers of polyethyleneimine ethoxylated (PEIE) and aluminum-doped zinc oxide nanoparticles (AZO NPs). This strategy effectively minimizes device damage while improving stability and charge transport efficiency. As a result, the photodetectors achieved a responsivity of 8 A/W, a detectivity of 12.28 x 1013 Jones, rise and delay times of 11.3 ms and 15.2 ms, respectively, and long-term stability for up to 25 days under ambient conditions (room temperature, RH = 60 %). These results demonstrate the potential of the proposed approach to advance MHP based photodetectors in diverse optoelectronic applications.
Reconstructed epidermal equivalents (REEs) consist of two distinct cell layers – the stratum corneum (SC) and the keratinocyte layer (KL). The interplay of these layers is particularly crucial in pruritic inflammatory disorders, like psoriasis, where a defective SC barrier is associated with immune dysregulation. However, independent evaluation of the skin barrier function of the SC and KL in REEs is highly challenging because of the lack of quantitative methodologies that do not disrupt the counter layer. Here, a non‐invasive impedance spectroscopy technique is introduced for dissecting the distinct contributions of the SC and KL to overall skin barrier function without disrupting the structure. These findings, inferred from the impedance spectra, highlight the individual barrier resistances and maturation levels of each layer. Using an equivalent circuit model, a correlation between impedance parameters and specific skin layers, offering insights beyond traditional impedance methods that address full‐thickness skin only is established. This approach successfully detects subtle changes, such as increased paracellular permeability due to mild irritants and the characterization of an immature SC in psoriatic models. This research has significant implications, paving the way for detailed mechanistic investigations and fostering the development of therapies for skin irritation and inflammatory disorders.
Lipid-based nanocarriers have been extensively utilized for the solubilization and cutaneous delivery of water-insoluble active ingredients in skincare formulations. However, their practical application is often limited by structural instability, leading to premature release and degradation of actives. Here we present highly robust multilamellar nanovesicles, prepared by the polyionic self-assembly of unilamellar vesicles with hydrolyzed collagen peptides, to stabilize all-trans-retinol and enhance its cutaneous delivery. Our results reveal that the reinforced multilayer structure substantially enhances dispersion stability under extremely harsh conditions, like freeze-thaw cycles, and stabilizes the encapsulated retinol. Interestingly, these multilamellar vesicles exhibit significantly lower cytotoxicity to human dermal fibroblasts than their unilamellar counterparts, likely due to their smaller particle number per weight, minimizing potential disruptions to cellular membranes. In artificial skin models, retinol-loaded multilamellar vesicles effectively upregulate collagen-related gene expression while suppressing the synthesis of metalloproteinases. These findings suggest that the robust multilamellar vesicles can serve as effective nanocarriers for the efficient delivery and stabilization of bioactive compounds in cutaneous applications.
Titanium dioxide (TiO2) nanoparticles are extensively used as a sunscreen filter due to their long-active ultraviolet (UV)-blocking performance. However, their practical use is being challenged by high photochemical activities and limited absorption spectrum. Current solutions include the coating of TiO2 with synthetic polymers and formulating a sunscreen product with additional organic UV filters. Unfortunately, these approaches are no longer considered effective because of recent environmental and public health issues. Herein, TiO2-metal-phenolic network hybrid nanoparticles (TiO2-MPN NPs) are developed as the sole active ingredient for sunscreen products through photochemical suppression and absorption spectrum widening. The MPNs are generated by the complexation of tannic acid with multivalent metal ions, forming a robust coating shell. The TiO2-MPN hybridization extends the absorption region to the high-energy-visible (HEV) light range via a new ligand-to-metal charge transfer photoexcitation pathway, boosting both the sun protection factor and ultraviolet-A protection factor about 4-fold. The TiO2-MPN NPs suppressed the photoinduced reactive oxygen species by 99.9% for 6 h under simulated solar irradiation. Accordingly, they substantially alleviated UV- and HEV-induced cytotoxicity of fibroblasts. This work outlines a new tactic for the eco-friendly and biocompatible design of sunscreen agents by selectively inhibiting the photocatalytic activities of semiconductor nanoparticles while broadening their optical spectrum.
Carbon nitride (CN) has emerged as a promising photocatalyst, recognized for its visible-light sensitivity, high conduction band-edge position, tunable electronic configuration, and environmental friendliness. Despite these attributes, the practical application of CN is hindered by challenges such as inefficient charge carrier separation, a narrow light absorption range, and inherent n-type characteristics due to nonstoichiometry. Here, we introduce a new postsynthetic functionalization strategy that modifies CN with catechol quinone (CQ) to substantially improve its photocatalytic performance through light-induced electron polarization and extended light absorption. The key mechanism involves promoted spatial charge separation at the CN-CQ interface, leveraging the light-triggered oscillation of CQ between its electron donor and acceptor states, corroborated by density functional theory calculations. Moreover, CN-CQ conjugation broadens the photoactive range of CN across the full spectrum of visible light due to lower-energy electronic excitations arising from the midgap states introduced by CQ. Under sunlight illumination, the CN-CQ conjugation increased the photocatalytic activities of CN 2-fold for photochemical gold ion reduction and hydrogen evolution. Our findings suggest that postsynthetic functionalization with a redox-active moiety is a promising strategy for enhancing the photocatalytic activity of CN.
MicroRNAs (miRNAs) serve as emerging biomarkers for a range of diseases, and their quantitative analysis draws increasing attention. Yet, current invasive methods limit continuous tracking within living cells. To overcome this, a nonenzymatic DNA-based nanoprobe is developed for dynamic, noninvasive miRNA tracking via live-cell imaging. This probe features a unique hairpin DNA structure with five guanines that act as internal quenchers, suppressing fluorescence from an attached fluorophore via photoinduced electron transfer. Target miRNA initiates toehold-mediated strand displacement, restoring, and amplifying the fluorescence signal. Additionally, by introducing a single mismatch to the hairpin DNA, the nanoprobe's sensitivity is significantly enhanced, lowering the detection limit to about 60 pM without compromising specificity. To optimize intracellular delivery for prolonged monitoring, the nanoprobe is encapsulated within multilamellar lipid nanovesicles, fluorescently labeled for dual-wavelength ratiometric analysis. The proposed nanoprobe demonstrates a significant advance in live-cell miRNA detection, promising enhanced in situ analysis for a better understanding of miRNAs' pathophysiological function.
Solar water oxidation is a crucial process in light-driven reductive synthesis, providing electrons and protons for various chemical reductions. Despite advances in light-harvesting materials and cocatalysts, achieving high efficiency and stability remains challenging. In this study, we present a simple yet effective strategy for immobilizing natural photosystems (PS) made of abundant and inexpensive elements, using amine-rich polyethylenimine (PEI) hydrogels, to fabricate organic/inorganic hybrid photoanodes. Natural PS II extracted from spinach was successfully immobilized on inverse opal TiO2 photoanodes in the presence of PEI hydrogels, leading to greatly enhanced solar water oxidation activity. Photoelectrochemical (PEC) analyses reveal that PS II can be immobilized in specific orientations through electrostatic interactions between the positively charged amine groups of PEI and the negatively charged stromal side of PS II. This specific orientation ensures efficient photogenerated charge separation and suppresses undesired side reactions such as the production of reactive oxygen species. Our study provides an effective immobilization platform and sheds light on the potential utilization of PS II in PEC water oxidation.
Lipid vesicles are widely used for drug and gene delivery, but their structural instability reduces in vivo efficacy and requires specialized handling. To address these limitations, strategies like lipid cross-linking and polymer-lipid conjugation are suggested to enhance stability and biological efficacy. However, the in vivo metabolism of these altered lipids remains unclear, necessitating further studies. A new stabilization technique without chemical modification is urgently needed. Here, a bio-mimetic approach for fabricating robust multilamellar lipid vesicles to enhance in vivo delivery and stabilization of protein antigens is presented. This method leverages 1-O-acylceramide, a natural skin lipid, to facilitate the self-assembly of lipid nanovesicles. Incorporating 1-O-acylceramide, anchoring lipid bilayers akin to its role in the stratum corneum, provides excellent stability under environmental stresses, including freeze-thaw cycles. Encapsulating ovalbumin as a model antigen and the adjuvant monophosphoryl lipid A demonstrates the vesicle's potential as a nanovaccine platform. In vitro studies show enhanced immune responses with both unilamellar and multilamellar vesicles, but in vivo analyses highlight the superior efficiency of multilamellar vesicles in inducing higher antibody and cytokine levels. This work suggests ceramide-induced multilamellar lipid vesicles as an effective nanovaccine platform for enhanced antigen delivery and stability.
Photothermal cancer therapy has gained increasing attention as a minimally invasive treatment via the localized heating of photothermal agents to eradicate cancer cells. However, its clinical translation has been limited...
Photothermal cancer therapy has gained increasing attention as a minimally invasive treatment via the localized heating of photothermal agents to eradicate cancer cells. However, its clinical translation has been limited by insufficient photothermal conversion in the near-infrared (NIR) range and low tumor-targeting efficiency. Here, synthetic melanin-like nanoparticles (similar to 190 nm in diameter) decorated with a cluster of smaller gold nanoparticles (similar to 20 nm in diameter) are developed as efficient NIR photothermal agents for in vivo cancer treatment. The melanin-gold hybrid nanoparticles are prepared by the oxidative polymerization of dopamine into colloidal melanin-like nanoparticles, followed by the spontaneous reduction of gold ion precursors into plasmonic nanoparticles on the surface of melanin nanoparticles. The gold nanoparticles significantly increase the NIR light absorption and photothermal conversion of the melanin nanoparticles, making their overall photothermal performance superior to conventional gold nanorods. Chemical conjugation of epidermal growth factor to the hybrid nanoparticles facilitates their cellular internalization into lung adenocarcinoma cells and enables in vivo tumor-targeting in a xenograft mouse model. The nanoparticles also exhibit excellent dispersion stability in serum and maintain high photothermal efficiency even after extensive laser irradiation. Our results suggest that the electronic hybridization of melanin and gold nanostructures provides a new opportunity to fine-tune their optical and chemical properties for tumor-targeted photothermal therapy.
The escalating demand and dwindling reserves of precious metals request efficient recycling techniques from electron waste. Addressing this need, we introduce a new method utilizing tannin-grafted mesoporous silica for the sunlight-boosted recovery of precious metals. Our strategy leverages the inherent photoreactivity of tannins, enabling metal-ligand complexation and plasmonic enhancement of chemical reduction. The result is a marked increase in the adsorption capacity and the high selectivity towards precious metal ions in electronic waste. Our robust covalent bonding approach concentrated tannic acids onto silica at a high density (500,000 per square micrometer), which significantly boosted the adsorption of gold ions up to an 11-fold increase, even amidst a mixture of nine other metal species. Impressively, we achieved a maximum adsorption capacity of 68.4 mmol per gram, equivalent to 13.4 g of gold per gram of adsorbent. Also, the adsorption rates for platinum and palladium ions were enhanced by 2.6 and 3.0 times, respectively. The underlying mechanism includes the visible-lightdriven plasmonic hot electron transfer that affords nearly perfect selectivity for gold ions (approximately 99%). These findings not only advance the field of metal recovery from electronic waste but also offer an environmentally benign and cost-effective solution that harnesses renewable solar energy.
The extracellular lipid matrix in the stratum corneum (SC) plays a critical role in skin barrier functionality, comprising three primary components: ceramides, cholesterol, and free fatty acids. The diverse ceramides, differentiated by molecular structures such as hydroxylations and varying chain lengths, are essential for the lipid matrix's structural integrity. Recently, a new subclass of ceramide, 1-O-acylceramide NP (CerENP), has been identified; however, its precise role in the lipid matrix of the SC is still elusive. Herein, we investigate the role of CerENP on the structure and permeability of the SC using molecular dynamics simulations. Our findings indicate that CerENP contributes to a compact lipid matrix in the lateral dimension of our SC model with a repeat distance of about 13 nm. Additionally, ethanol permeability assessments show that CerENP effectively reduces molecular penetration through the lipid matrix. This study provides an insight into the role of a new subclass of ceramide in the SC, enhancing our understanding of skin structure and the mechanisms behind barrier dysfunction in skin diseases.
In solar water splitting, the poor chemical and mechanical durability of photoanode materials under oxidative environments has been raised as a crucial issue. Despite promising water oxidation activity, the stable immobilization of polyoxometalates (POMs) onto photoanodes is very challenging. Here we report sustainable photoelectrochemical water oxidation through the deposition of catalytic POMs onto a plasmonic Au/TiO2 photoanode, followed by the atomic layer deposition of a thin Al2O3 layer. Vacuum deposition techniques were used with polystyrene nanospheres as sacrificial templates to fabricate an Au/TiO2 half-shell array as a photoanode with strong plasmonic absorption and excellent stability in aqueous media. The thin Al2O3 layer serves as a protective layer for [Co4(H2O)2(PW9O34)2]10- (Co4POMs) attached to Au/TiO2 half-shells functionalized with cysteamines. The Al2O3 layer increased the photocurrent and delayed current attenuation by preventing the dissociation of Co4POMs from the surface during the water oxidation. A thicker Al2O3 layer exhibited a higher protection effect but reduced the catalytic activity of Co4POMs in the early stage of water oxidation due to the limited exposure of Co4POMs to electrolytes. Furthermore, regardless of the POMs, the Al2O3 layer also passivated the TiO2 surface, improving electron transfer through the POMs/Au half-shell structure. This work suggests that the catalyst/plasmonic photoelectrode with a thin protection layer is a promising alternative to conventional semiconductor-based photoelectrodes for sustainable and efficient water oxidation.
Base-Pair Mismatch In article 2202076, Yoon Sung Nam and co-workers develop a new miRNA detection platform based on miRNA-catalyzed toehold-mediated strand displacement and the sequential formation of DNA-streptavidin nanogel. The detection limit is lowered from the nanomolar level to the picomolar level by introducing a single base-pair mismatch near the toehold enhancing strand displacement and generating a 3D nanogel network to facilitate Förster resonance energy transfer.
Plasmonic catalysts have the potential to accelerate and control chemical reactions with light by exploiting localized surface plasmon resonances. However, the mechanisms governing plasmonic catalysis are not simple to decouple. Several plasmon-derived phenomena, such as electromagnetic field enhancements, temperature, or the generation of charge carriers, can affect the reactivity of the system. These effects are convoluted with the inherent (nonplasmonic) catalytic properties of the metal surface. Disentangling these coexisting effects is challenging but is the key to rationally controlling reaction pathways and enhancing reaction rates. This study utilizes super-resolution fluorescence microscopy to examine the mechanisms of plasmonic catalysis at the single-particle level. The reduction reaction of resazurin to resorufin in the presence of Au nanorods coated with a porous silica shell is investigated in situ. This allows the determination of reaction rates with a single-molecule sensitivity and subparticle resolution. By variation of the irradiation wavelength, it is possible to examine two different regimes: photoexcitation of the reactant molecules and photoexcitation of the nanoparticle's plasmon resonance. In addition, the measured spatial distribution of reactivity allows differentiation between superficial and far-field effects. Our results indicate that the reduction of resazurin can occur through more than one reaction pathway, being most efficient when the reactant is photoexcited and is in contact with the Au surface. In addition, it was found that the spatial distribution of enhancements varies, depending on the underlying mechanism. These findings contribute to the fundamental understanding of plasmonic catalysis and the rational design of future plasmonic nanocatalysts.