Oxidative stress can hinders tissue regeneration, thus highlighting the importance of localized antioxidant-based interventions. Herein, we engineered a synergistic skin delivery platform that combined idebenone (IDB)-loaded anti-oxidative mesoporous polydopamine nanoparticles (mPDA) with dissolving microneedles (MNs) for localized anti-oxidative stress treatment. Through a soft-template synthesis, the mPDA nanocarrier was prepared, achieving a drug loading of 5.00% ± 0.26% and encapsulation efficiency of 88.36% ± 3.85%. Based on a central composite design-response surface methodology (CCD-RSM), the PVP/PVA‑based MN was optimized with robust mechanical strength to accommodate nanoparticles for skin penetration. The platform substantially enhanced the penetration depth in the skin by formation of microchannels for deep dermal delivery. Synergistic antioxidant activity was achieved, respectively scavenging 80.96% ± 4.71% DPPH radicals and 49.89% ± 4.32% hydroxyl radicals, while also greatly reducing intracellular ROS in H₂O₂-stressed PC12 cells. Additionally, it increases the neuronal differentiation rate and neurite length to two-fold, while also promoting keratinocyte migration for wound healing. This nanocomposite MN system provides enhanced localized drug delivery, combined antioxidant action, and simulation of tissue regeneration, offering a promising strategy for treatment of oxidative stress-impaired conditions.

Hydrogen peroxide (H2O2) in skin tissue serves as a critical biomarker for oxidative stress and physiological status, yet its precise in situ monitoring remains challenging due to the lack of non-invasive, real-time sensing platforms. Herein, we presented a smartphone-assisted biosensing system based on a nanozyme-integrated hydrogel microneedle patch for on-site and quantitative detection of cutaneous H2O2. The sensing platform incorporated a palladium-embedded metal-organic framework (Pd-PCN) with enhanced peroxidase-like activity, which was co-immobilized with a chromogenic substrate in a polymeric composite hydrogel microneedle array. This composite matrix maintained structural integrity and biocompatibility during short-term skin application while providing an aqueous microenvironment favorable for nanozyme-catalyzed reactions. Upon insertion into the skin, H2O2 from interstitial fluid would diffuse into the microneedle and trigger a colorimetric reaction. The resulting color intensity could be quantitatively captured via smartphone-based RGB analysis. The system demonstrated a wide linear detection range (5-100 & micro;M), a low detection limit (1.53 & micro;M), high reproducibility (RSD < 5 %), and negligible interference from common biological substances. Confocal imaging and mechanical testing further confirm the structural stability and skin-penetration capability of the microneedle under operational conditions. This work established a reliable, minimally invasive, and user-friendly platform for continuous monitoring of oxidative biomarkers in skin, paving the way for personalized dermatological care and point-of-care diagnostics.

High-quality wound healing is a primary clinical goal, yet it remains difficult to achieve reliably with current treatments. For this purpose, this study developed an ion-paired asiatic acid (AA) hydrogel specially for wound healing and systematically evaluated its pharmacodynamic efficacy both in vitro and in vivo. The formulation strategy involved screening organic amines as counter-ions using an ex vivo stratum corneum-removed skin model. Triethanolamine was identified as the optimal counterion, maximizing AA penetration into local tissue while minimizing systemic permeation via the formation of an ion-pair as confirmed by Nuclear Magnetic Resonance. The resulting hydrogel exhibited ideal properties for wound application, as characterized by its water vapor transmission rate, swelling ratio, degradability ratio, and water retention. In vitro, the hydrogel accelerated wound closure by stimulating cellular proliferation and migration, promoting vascular differentiation, and exhibiting selective antibacterial efficacy against S. aureus. In a rat full-thickness skin defect model, the hydrogel effectively facilitated scarless healing, which was mechanistically linked to collagen remodeling (indicated by a higher proportion of type III relative to type I collagen), suppression of TNF-alpha-mediated inflammation, and downregulation of TGF-beta-driven fibrosis. Collectively, this work establishes a strategically designed ion-pair hydrogel system that coordinates key healing processes, offering a promising strategy for achieving reliable, high-quality wound regeneration.

Protein-based nanoparticles hold great promise for bioactive molecule delivery, but conventional fabrication routes are often complex and rely on surfactants or organic solvents. Here, we reported a crosslinker-free strategy to engineer α-lactalbumin (ALA) nanoparticles via Ca²⁺ mediated ionic bridging and electrospraying, enabling efficient encapsulation of acidic fibroblast growth factor (aFGF). These aFGF@ALA nanoparticles were subsequently integrated into electrospun poly(vinyl alcohol) (PVA) nanofiber matrices to construct hybrid dressings (aFGF@ALA NPs/PVA ENMs). The resulting nanostructures combine the structural support of nanofibers with the controlled release capacity of protein nanoparticles, yielding a synergistic platform for therapeutic delivery. In vitro, the hybrid dressings promoted fibroblasts and keratinocytes proliferation and migration with excellent cytocompatibility. In vivo, they accelerated burn wound repair by enhancing re-epithelialization, collagen I/III remodeling, and angiogenesis. This work introduces a facile and generalizable strategy for designing functional protein-based nanoparticles and demonstrates their integration with nanofiber scaffolds as a versatile platform for growth factor delivery and tissue regeneration.

Despite considerable advancements in pharmaceutical strategies (e.g., nanocarriers, physical enhancement) to overcome the skin barrier for topical photodynamic therapy (PDT), clinical translation remains impeded by unresolved challenges. While previous reviews have predominantly focused on enhancing photosensitizer permeation, this work shifts the paradigm to systematically address three critical yet under-reviewed barriers: insufficient spatiotemporal precision in photosensitizer delivery, hypoxia-induced therapeutic resistance, and inefficient photon utilization. This review critically evaluated the transformative evolution from conventional formulations toward “smart” therapeutic architectures, presenting a coherent framework of material-based solutions engineered to overcome these specific challenges: (1) depth-resolved, stimuli-responsive, and molecular-targeted release mechanisms; (2) transdermal oxygen self-replenishing systems (e.g., catalase-mimetic nanomaterials or perfluorocarbon-based reservoirs); and (3) synergistic optical components to enhance photon utilization, including tissue optical clearing agents, light-guiding channels, and multifunctional light-responsive platforms. These integrated strategies enable the dynamic synchronization of photosensitizer bioavailability with pathological microenvironmental demands, allowing precise modulation across spatial, temporal, and dosage dimensions. Furthermore, we incorporated an analysis of commercially available and clinically investigated photosensitizers, providing critical context for the current state and future trajectory of the field. By bridging interdisciplinary insights from materials science, drug delivery, and photobiology, this work outlines a transformative roadmap for next-generation, precision-based dermatological therapies, marking a clear departure from penetration-centric approaches.

Infected diabetic wounds face multiple challenges, including bacterial infection, uncontrolled inflammation, and impaired angiogenesis, leading to prolonged wound healing. However, traditional dressings for infected diabetic wounds lack effective antibacterial properties, cannot manage inflammatory exudate, or cannot monitor healing in real time. Hence, we propose a pH-monitoring self-pumping antibacterial microneedle dressing that simultaneously provides antibacterial activity, inflammatory exudate management, and wound status monitoring. The dressing consists of a pH-monitoring absorbent layer, an adhesive drainage layer, and an antimicrobial microneedle layer. The first two layers form a pH-monitoring self-pumping backing layer. The microneedle layer of this dressing punctures the MRSA biofilm in diabetic wounds and eradicates MRSA. The dissolved microneedle tips drain inflammatory exudate into the pH-monitoring self-pumping backing layer, where unidirectional drainage enables exudate removal and pH colorimetric monitoring to assess wound healing status. In MRSA-infected diabetic wound healing experiments and immunofluorescence analyses, this dressing demonstrates excellent antibacterial activity, inflammatory regulation, and vascular regeneration. This multifunctional integrated dressing offers a novel treatment paradigm for infected diabetic wounds.

Glioblastoma (GBM) is one of the most malignant and lethal primary brain tumors, and the blood-brain barrier (BBB) poses a significant challenge to its treatment. In this study, disulfiram-loaded Zein Janus nanoparticles (Lf/M2pep@ZEN-DSF) were developed using the Pickering emulsion method for enhanced GBM therapy. Lactoferrin (Lf) was modified to one side of the Janus nanoparticles to facilitate BBB penetration and GBM targeting, while M2pep peptides were modified to the opposite side for targeting tumor-associated macrophages (TAMs). The results demonstrated that Lf/M2pep@ZEN-DSF effectively crossed the BBB and targeted brain tissues. Additionally, the Janus nanoparticles selectively targeted M2-polarized TAMs via M2pep and repolarized them into the M1 subtype for GBM therapy. Furthermore, the Janus nanoparticles significantly enhanced intracellular reactive oxygen species (ROS) generation in GBM cells. In vivo studies confirmed that the nanoparticles significantly increased drug accumulation in the brain and prolonged the survival of GBM-bearing mice. Immunohistochemical analysis revealed that Lf/M2pep@ZEN-DSF treatment induced M2-to-M1 TAM repolarization, effectively remodeling the tumor immune microenvironment. These findings collectively indicate that Lf/M2pep@ZEN-DSF is a promising nanomedicine with favorable biosafety for enhanced GBM treatment.

Wound healing is a complex, multi-phase biological process that continues to pose significant challenges in biomedical engineering. As such, the development of innovative therapeutic strategies and sustainable, multifunctional biomaterials capable of accelerating tissue repair remains a top priority. In this study, we present a green, multiprotein nanofiber-based system fabricated via waterborne electrospinning using water as the sole solvent. The nanofibers, composed of α-lactalbumin (ALA) and soy protein isolate (SPI) with up to 90% (w/w) protein content, were formulated with minimal amounts of polyethylene oxide (PEO). Comprehensive analysis of nanofiber morphology, water stability, and mechanical properties revealed that the combination of ALA and SPI provided enhanced structural tunability and performance compared to single-protein systems. In a rat model of third-degree burns, the ALA/SPI/PEO nanofibers significantly improved wound healing outcomes relative to controls, as evidenced by accelerated re-epithelialization, increased collagen deposition, and enhanced angiogenesis; all this being attributable to the synergistic effects of the two protein components. By integrating sustainability, material design and therapeutic efficacy into a single platform, our multiprotein nanofiber system offers a compelling blueprint for the next generation of eco-conscious and clinically translatable biomaterials.

Sonodynamic therapy is an emerging therapeutic approach for combating bacterial infections. However, the characteristics of hypoxia, high H2O2 microenvironment, and the formation of persistent biofilms in diabetic wound sites limit its efficacy in this field. To address these issues, we developed a multifunctional antibacterial hydrogel dressing PPCN@Pt-AMPs/HGel with the cross-linked gelatin and sodium alginate as the matrix, where the nanosonosensitizer PCN-224 was decorated with the oxygen-generating Pt nanoenzyme and further coupled with a biofilm-targeting antimicrobial peptide via an interacting polydopamine layer. This nano-composite hydrogel displayed improved mechanical properties as well as good biocompatibility and biodegradability. The catalase-like activity of the nanoparticles facilitated the ultrasound-induced generation of the singlet oxygen due to the catalytic decomposition of the H2O2 into O2. In vitro results showed that the hydrogel dressing exhibited excellent antimicrobial ability under low-intensity ultrasound stimulation, which could effectively inhibit the newly formed biofilm and eliminate the full-grown biofilms. In the infected diabetic wound of rats, PPCN@Pt-AMPs/HGel significantly enhanced the wound healing rate under low-intensity ultrasound stimulation and improved the regeneration outcomes by promoting granulation tissue formation, angiogenesis, and type III collagen deposition. In conclusion, our study provides a novel and effective antibacterial hydrogel dressing for sonodynamic treatment of diabetic wounds.

Diabetes exhibits several long-term serious health complications, including healing-impaired wounds, which result in substantial clinical challenges, warranting the need to develop efficient wound dressings. Herein, multifunctional in situ hydrogels as diabetic wound dressings were accomplished by concomitant spraying of 3-aminophenyl boronic acid (PBA)- grafted dialdehyde laminarin (LamPBA) and silver nanoparticles-impregnated polyvinyl alcohol (PVA-AgNPs). The hydrogels with and without AgNPs (F2 and F1, respectively) conferred excellent rheological characteristics and acceptable antibacterial activity (up to 80 % reduction in survival) against E. coli and S. aureus. Cellular experiments revealed that the hydrogels obviously promoted the proliferation and migration of HaCaT and NIH/3 T3 cells. In diabetic mice, the hydrogels accomplished ~90 % wound closure by day 9, outperforming controls (65-70 %). Additionally, F1 and F2 considerably increased the CD206/CD86 ratio (46 ± 5 and 62 ± 7, respectively) compared to diabetic (0.6 ± 0.1) and nondiabetic (2 ± 0.2) controls. Moreover, the hydrogels demonstrated remarkably triggered epidermal tissue regeneration, collagen deposition, antioxidant defense and angiogenesis. The hydrogels containing AgNPs portrayed superior wound healing potential over AgNP-free hydrogels. Overall, the in situ hydrogels (LamPBA/PVA-AgNPs, F2) could augment the diabetic wound healing rates in an effective manner and be utilized as promising wound care biomaterials.

BACKGROUND:Over the recent years, the investigations on wound dressings have been undergoing significant evolution, and now smart dressings with the function of the real-time monitoring of the wound states have been recognized as one of the most advanced treatment modalities. Among a variety of wound-related biomarkers, pH represents a promising candidate for in situ supervising the wound healing status. In this regard, a variety of optically pH sensing agents have been widely incorporated into different types of wound dressings. RESULTS:Herein, we first presented an overview of the advanced wound dressings, especially those commonly used in wound pH sensing. Then, a comprehensive summary of the optical pH sensing agents that could be incorporated into the wound dressings for detecting the pH alteration on the wound bed was described in detail. These materials were classified into colorimetric dyes (i.e., synthetic and plant-based dyes) and fluorescent probes (i.e., small-molecular fluorescein and fluorescent nanomaterials). Each type of pH sensing agent was fully discussed with advantages and limitations for monitoring the wound pH alteration, as well as typical examples of practical applications. To well interpret messages produced by the color-coding dressings, the approaches for defining and communicating color were also summarized, and a proof-of-concept, the smartphone-based remote supervision was particularly highlighted. SIGNIFICANCE:This review provides a comprehensive overview of the utilization of optically pH sensing in advanced wound dressings for the real-time monitoring of the wound states. It was expected to be an informative source for the exploitation of novel diagnostic dressings for wound management, and also a reference the for application of these materials in the biosensing of other physiological or pathological fluids.

Activation of the stimulator of interferon genes (STING) pathway holds immense potential for cancer immunotherapy. However, clinical translation of STING agonists such as cyclic GMP-AMP (cGAMP) is hindered by their inherent instability and poor cellular uptake efficacy. Herein, we report an iron oxide nanoparticle (IONP)-based carrier for delivering cGAMP via coordination chemistry. The ribose, phosphate, and adenine on cGAMP were leveraged to directly bind IONP, resulting in cGAMP-functionalized IONPs (Fe-cGAMP). Such a design greatly improved the cellular uptake and STING activation efficacy of cGAMP. Beyond delivery, IONPs promoted reactive oxygen species (ROS) production and activated Toll-like receptors, leading to synergistic immune activation alongside cGAMP. Fe-cGAMP exhibited robust antitumor effects in multiple mouse tumor models. In combination with immune checkpoint inhibitors, Fe-cGAMP could induce complete tumor remission in over 50% of treated mice, and these mice also remain tumor-free upon a subsequent challenge, demonstrating strong and long-lasting antitumor immune responses.

Heavily exuding wounds are difficult to heal due to the accumulation of a large amount of exudates and the difficulty in efficient delivery of drugs by conventional wound dressings. Herein, inspired by the microstructure and function of octopus sucker (OS) and tree trunk (TT), we propose a bioinspired strategy to fabricate novel bioinspired OS&TT bilayered wound dressing, assembled by a lower OS-like nanofiber membrane with concave convex arrays and an upper TT-like nanofiber sponge with vertically aligned pores. The integration of bioinspired concave arrays and vertically aligned pores endows the bioinspired OS&TT dressing with dual vertical suction property, enabling effective drainage of significant amount of accumulated liquid. Moreover, the bioinspired convex arrays facilitate distinct drug reverse delivery, achieving a drug delivery efficiency exceeding 88.27 %. In vivo heavily exuding wound treatment results indicate that, the bioinspired OS&TT dressing can alleviate tissue edema, decrease the contents of proinflammatory cytokines, and accelerate wound healing due to the unique dual vertical suction of exudates. When treating the bacteria-infected wound, benefiting from the reverse delivery of antimicrobial ε-polylysine to efficiently kill bacteria, the bioinspired OS&TT dressing shows a better wound healing effect than the dressing with inefficient drug delivery capacity.

Chiral beta-hydroxy sulfones are important chiral building blocks for the synthesis of pharmaceutical products and fine chemicals. Herein, the synthesis of chiral beta-hydroxy sulfones through a photo-biocatalytic cascade reaction is described. The photocatalyst sodium anthraquinone-2-sulfonate (SAS) was firstly employed to prepare beta-keto sulfones by constructing C-S and C-O bonds, and then, a wide variety of chiral beta-hydroxy sulfones were synthesized with high stereoselectivity (up to >99 % ee) and moderate to high yields (63 %similar to 89 %) by coupling this light-driven reaction with an enzymatic process in one pot. This strategy is proved to be effective and practical, which promises to inspire additional perspectives for the synthesis of chiral beta-hydroxy sulfones in a green manner.

OBJECTIVE:To examine the effect of Xuanfei Tongqiao acupuncture on nasal inflammation in rats with allergic rhinitis (AR) and its underlying mechanisms, particularly focusing on the role of acupuncture in regulating the methylation of long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5). METHODS:Interventions involved acupuncture or short hairpin RNA-GAS5 (sh-GAS5) lentivirus in an ovalbumin-induced AR rat model. Nasal mucosal tissues were collected post-intervention for pathological analysis. Parameters assessed included the proportion of type 2 innate lymphoid cells (ILC2s), the expression of GATA binding protein 3 (GATA3), methyltransferase-like 3 (METTL3), interleukin (IL)-33 proteins, and the expression of METTL3 and lncRNA-GAS5. RESULTS:Xuanfei Tongqiao acupuncture and/or lentivirus sh-GAS5 significantly alleviated rhinitis symptoms and reduced nasal inflammation in AR rats. This was evidenced by a reduction in inflammatory cells, eosinophils, and cuprocytes in nasal mucosal tissues, along with a decreased proportion of ILC2s. Furthermore, protein levels of GATA3, METTL3, and IL-33, as well as the expression of METTL3 and lncRNA-GAS5, were significantly reduced. These findings suggest that lncRNA-GAS5 and its N6-methyladenosine methylation are key regulators of AR inflammation, with acupuncture exerting a modulatory effect on this pathway. CONCLUSIONS:Xuanfei Tongqiao acupuncture therapy inhibited the METTL3-GAS5-GATA3-IL-33-ILC2 pathway, reducing the inflammatory response and alleviating nasal symptoms in AR rats. These results suggest that Xuanfei Tongqiao acupuncture could serve as a potential alternative therapy for preventing and managing AR associated with inflammation.

Sonodynamic therapy (SDT) is a novel therapeutic modality that is effective for the noninvasive treatment of dermatological diseases. As a ubiquitous large class of sonosensitizers, however, porphyrins suffer from poor skin permeability and the inefficient generation of reactive oxygen species. Herein, different-sized porphyrinic metal-organic frameworks (MOFs), PCN-224 (90, 125, and 200 nm), were developed via the coordination of tetra-kis(4-carboxyphenyl) porphyrin (TCPP) and the metal zirconium to enhance the local delivery of porphyrins, and fluorescent sonosensitizers (methylene blue or rhodamine 6G) were further incorporated to improve the sonodynamic effect, as well as to visualize the delivery of PCN-224 and its cargo. The skin penetration of PCN-224 was found to be increased with the reduction of particle size, and all three-sized samples could overcome the barrier of stratum corneum, even achieving the dermis of the porcine skin. Both intercellular and follicular pathways were noticed for three-sized PCN-224, while the follicular one played a more significant role in the penetration of the smallest PCN-224. The intact nanoparticles were found in the skin. At the initial stage, the nanoparticle and its cargo penetrated the skin as an intact entity, while the encapsulated rhodamine 6G was slowly released to the microenvironment of the skin from the nanoparticle with the prolongation of application. The combination of PCN-224 and methylene blue could increase the acoustically triggered generation of O-1(2), distinctly boosting the lethal effect against the cancerous cell. Collectively, the study revealed the feasibility of PCN-224 for topical use, suggested an innovative method to enhance the sonodynamic effect, and proposed a possible mechanism for skin drug delivery of MOFs.

The development and application of novel polysaccharides that can improve diabetic wound healing is crucial. Dressings containing curdlan have the potential to promote healing in diabetic wounds, but the underlying mechanism remain unclear. In addition, the functional modifications that could further enhance the activity of curdlan in promoting diabetic wound healing have not been explored. Herein, we investigated the capabilities of curdlan (CU) and its four derivatives i.e., sulfated curdlan (SC), amino-curdlan (AC) carboxymethyl curdlan (CMC) and CMC/ZnO nanocomposites for diabetic wound healing. Pristine CU and its derivatives were blended with polyvinyl alcohol (PVA) to fabricate electrospun nanofiber dressings (ENDs) with uniform appearances. The PVA/CU, PVA/CMC and PVA/CMC-ZnO ENDs were more compatible with keratinocytes, fibroblasts, and macrophages than that of PVA/AC ENDs. Notably, PVA/CMC ENDs and PVA/CMC-ZnO ENDs exhibited superior wound healing efficiencies than other ENDs. Among various dressings, PVA/CU, PVA/SC, PVA/CMC ENDs effectively reduced M1 macrophages and facilitated M2 phenotype at early stage of diabetic wound healing. Collectively, the PVA/CMC ENDs demonstrated greater therapeutic potential against diabetic wounds compared to other modified scaffolds via regulating macrophage polarization.

Introduction:The effect of traditional treatment for melanoma is quite limited, especially for its recurrence. As the major components of yeast cell wall, chitin and β-glucan exhibit good immune activation effect and are promising candidates for adjuvant. Therefore, melanoma cell membrane (CM) and indocyanine green (ICG) was loaded in a chitin and β-glucan hybrid hydrogel to achieve an enhanced anti-melanoma therapy.Methods:The novel hybrid hydrogel was prepared, and its physicochemical properties were examined. Its effect towards melanoma prevention and treatment was evaluated via a melanoma-bearing mice model.Results:The CM-ICG-hybrid hydrogel was successfully prepared with excellent injectability, self-healing, drug loading, rheological, in vitro and in vivo photothermal stability, and retention properties. It also exhibited good cellular and in vivo safety profiles. In the primary melanoma mice model, it quickly ablated the in-situ melanoma, effectively inhibited the tumor growth, increased the survival rate of melanoma-bearing mice, and increased the level of IFN-γ and TNF-α. In the distal secondary melanoma model, it efficiently prevented the reoccurrence of melanoma and activated the memory T cells. In both models, a synergistic effect of photothermal therapy and immune therapy was found. The hydrogel effectively recruited CD3+ CD4+ T cells and CD3+ CD8+ T cells, inhibited the proliferation of melanoma cells, and induced the apoptosis of melanoma cells.Conclusion:The hybrid hydrogel was successfully prepared, and it showed excellent efficacy towards melanoma prevention and treatment due to its efficient tumor ablation and immune activation capability.