Biomaterials Advances
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2026
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IF 6.7
Yuzhou Chen,Zidi Yan,Meng Zhu,Yu Liu,Kejia Li,Le Yue,Ye Tian,Hongyan Xiao,Liping Wen,Zhongwei Niu
2,3-Catechol shows superior antioxidant property and oxidation resistance than 3,4-isomer. • An innovative fabrication strategy for a chitosan hydrogel is established. • A new therapeutic option for granulation regeneration in diabetic wounds is provided. Diabetic wound healing remains a major clinical challenge due to a pathological microenvironment characterized by excessive reactive oxygen species (ROS) and chronic inflammation. Excessive ROS through multiple distinct pathways hinders the regeneration of granulation tissue, which is the essential scaffold for wound repair. Although catechol attracted considerable interest for antioxidant applications in biomaterials, its inherent chemical instability under physiological conditions severely limits its therapeutic potential and clinical applications. To address these critical challenges, an antioxidant 2,3-HCat-CS/STPP hydrogel has been developed via the freeze-thaw method, composed of 2,3-dihydroxybenzoic acid modification of chitosan (2,3-HCat-CS) and sodium tripolyphosphate (STPP). As an antioxidant, 2,3-HCat-CS was demonstrated both theoretically and experimentally to possess superior oxidative stability and ROS-scavenging property compared to the conventional 3,4-isomer. Exploration of the gelation mechanism revealed that 2,3-HCat-CS/STPP hydrogel is formed from electrostatic interactions, crystalline regions and hydrogen bonds. Hydrogel exhibited excellent antioxidant property and biocompatibility in vitro . In a full-thickness wound model in db/db mice, treatment with 2,3-HCat-CS/STPP hydrogel effectively reduced local ROS levels, mitigated inflammation and increased the levels of key anti-inflammatory cytokines (TGF-β1 and IL-10). This intervention effectively disrupted the detrimental inflammatory cycle characteristic of diabetic wounds, thereby fostering the process of angiogenesis and granulation regeneration. This work combines the molecular design of catechol and the fabrication process of chitosan gelation to create 2,3-HCat-CS/STPP hydrogel that promotes granulation regeneration in diabetic wounds, which presents a potential therapeutic platform for chronic wounds management. Download: Download high-res image (294KB) Download: Download full-size image
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MATERIALS & DESIGN
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2026
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IF 8.2
Ziwei Li,Qiuying Wu,Rui Ni,Jingjing Wang,Meiyang Yang,Wenyuan Zhang,Jiaming Li,Dan Peng,Lin Song,Yao Liu
Qu@NPs/ADSCs@CS-gel integrates anti-inflammatory, antibacterial, immunomodulatory properties for infected wound healing. • Hydrogel with genipin-crosslinked chitosan/silk sericin, encapsulated ADSCs, and surface-attached ROS-responsive Qu@NPs. • Qu@NPs release quercetin in response to ROS, effectively scavenging ROS and reducing inflammation while preserving SOD activity. • Hydrogel inhibits M1 polarization & inflammatory cytokines, promotes M2 transition & creates regenerative microenvironment. • Enhances antibacterial, proliferation, re-epithelialization, angiogenesis, collagen deposition, accelerates wound repair. Chronic infected wounds face healing challenges due to the interplay of persistent infection, excessive inflammation, and impaired angiogenesis. Conventional dressings often address only one pathological aspect, resulting in limited therapeutic effects. To overcome these barriers, we developed a multifunctional hydrogel Qu@NPs/ADSCs@CS-gel that integrates anti-inflammatory, antibacterial, and immunomodulatory activities. The system was fabricated from genipin-crosslinked chitosan and silk sericin into a biocompatible hydrogel (CS-gel) that exhibits antibacterial activity and permits cellular matrix permeability. Adipose-derived stem cells (ADSCs) were encapsulated within this hydrogel, while reactive oxygen species (ROS)-responsive quercetin-loaded nanoparticles (Qu@NPs), based on poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG), were attached to its surface. Upon wound contact, Qu@NPs are released from Qu@NPs/ADSCs@CS-gel, and PPS-PEG breaks down in response to ROS to release quercetin, effectively eliminating ROS and alleviating the inflammatory response, thereby establishing a regenerative microenvironment for ADSC-mediated repair. Qu@NPs/ADSCs@CS-gel exhibited potent antibacterial activity, reduced ROS accumulation in macrophages while preserving superoxide dismutase (SOD) activity. Furthermore, it inhibited M1 macrophage polarization and pro-inflammatory cytokine secretion, while promoting transition to the M2 phenotype. These effects collectively improved cell proliferation, re-epithelialization, angiogenesis, and collagen deposition, accelerating the three phases of wound repair. Our findings support Qu@NPs/ADSCs@CS-gel as an advanced dressing for infected wounds.
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Nature Communications
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2026
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IF 18.1
Huang Kai,Liu Hui-Zhi,Liu Yuan,Lyu Jia-Yan,Zhang Qing-Yi,Feng Zi-Yuan,Wang Zi-Lin,Dong Hui,Nie Rong,Zhang Yi-Wen,Zhang Yue-Qi,Zeng Yi,Xie Hui-Qi,Zhou Zhou,Shen Bin
Osteoarthritis (OA) remains difficult to treat because drug transport within cartilage is restricted by its dense extracellular matrix and rapid joint clearance. Here we show that hybrid exosomal nanomotors (CAP-Mn/140@hyExos) convert pathological reactive oxygen species (ROS) into transport-driving cues to overcome diffusion-limited transport within cartilage. In the oxidative OA microenvironment, manganese dioxide (MnO₂) catalyzes H₂O₂ decomposition, driving ROS-responsive transport, while a cartilage-targeting peptide enhances matrix interaction, together promoting cartilage accumulation. This strategy achieves deeper penetration (~140 μm), greater cellular uptake (~2.5-fold), and prolonged intra-articular retention (~30% remaining at two weeks). Enhanced transport enables efficient intracellular delivery of miR-140 and MnO₂ nanoparticles, attenuating oxidative stress and promoting cartilage regeneration. In a rat OA model, this therapeutic strategy improves gait performance, restores subchondral bone microarchitecture, and suppresses OA progression. These findings establish pathological microenvironments as endogenous drivers of intratissue drug transport, providing a transport-regulated strategy for drug delivery in transport-restricted tissues.
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Frontiers in Pharmacology
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2026
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IF 5.4
Yanqing Wu,Xilin Qiao,Shuaiyu Chen,Yalan Lu,Bingyan Mao,Mengdie Zhu,Xinzhi Chen,Nipi Chen,Zhishan Ding,Bo Jin
Introduction MicroRNA-29b-3p (miR-29b-3p) plays a critical role in regulating endothelial apoptosis and autophagy. We previously demonstrated that protocatechualdehyde (PCA), a water-soluble phenolic acid derived from Salvia miltiorrhiza Bge., protects human umbilical vein endothelial cells (HUVECs) against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury. However, whether miR-29b-3p mediates this protective effect remains unclear. Methods Using the OGD/R in vitro model of ischemia-reperfusion injury, we investigated the molecular mechanisms underlying ischemic damage at the cellular level. RT-qPCR was used to measure miR-29b-3p expression, Western blotting to assess autophagy- and apoptosis-related proteins, and MDC staining and flow cytometry to evaluate autophagy and apoptosis, respectively. Results The results showed that miR-29b-3p was downregulated in OGD/R-treated HUVECs, an effect that was reversed by PCA and the ROS inhibitor N-acetylcysteine (NAC). The miR-29b-3p mimic enhanced the promoting effects of PCA and NAC on miR-29b-3p expression, whereas miR-29b-3p inhibitor reversed these effects. Similarly, PCA-induced autophagy and inhibition of apoptosis were enhanced by the miR-29b-3p mimic and reversed by the inhibitor. To determine whether SIRT1 acts downstream of miR-29b-3p, we used EX527 (a SIRT1 inhibitor) and found that it attenuated the PCA-mediated upregulation of miR-29b-3p. The miR-29b-3p mimic enhanced PCA-induced SIRT1 activity and protein expression, while the inhibitor had the opposite effect. Additional experiments revealed that NAC suppressed ROS by upregulating miR-29b-3p, leading to increased SIRT1 expression and reduced apoptosis. Disscussion Collectively, these findings demonstrate that PCA ameliorates OGD/R-induced endothelial injury by promoting autophagy and inhibiting apoptosis via the ROS/miR-29b-3p/SIRT1 regulatory axis.
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JOURNAL OF CONTROLLED RELEASE
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2026
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IF 12.4
Chang Peng,Bing Han,Qiao Qu,Aiyang Tong,Siqi Wang,Ji Li,Dalu Wang,Yang Ge
Pyroptosis-induced production of inflammatory cytokines and elevated levels of cell-free DNA (cfDNA) are major pathogenic drivers of intestinal inflammatory diseases. Inflammatory macrophages perform a vital role in mediating inflammatory immune responses, and their targeted modulation represents a promising therapeutic strategy for colitis. Cationic nanoparticles possess considerable therapeutic promise in inflammatory disorders due to their high affinity for cfDNA. In this work, we established a combinatorial therapeutic strategy using reactive oxygen species (ROS)-responsive cationic nanoparticles that simultaneously scavenge cfDNA and transport 4-octyl itaconate (4-OI), a potent agent against pyroptosis. This dual-functional nanosystem effectively rebalances the inflammatory microenvironment by suppressing pyroptosis and neutralizing cfDNA in colonic tissues. The nanoparticles exhibited excellent biocompatibility and robust therapeutic efficacy in the context of experimental IBD in mice, with sustained drug release triggered by ROS overexpression in inflamed regions. Notably, this approach demonstrates minimal cytotoxicity and leads to substantial amelioration of disease pathology, offering an innovative therapeutic approach for the targeted control of inflammatory diseases through the coordinated targeting of multiple pathological axes.
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Materials Today Communications
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2026
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IF 4.9
Xinchen Du,Yafang Chen,Peng Zhang,Xuelei Li,Jilite Wang,Sheng Yang,Binhong Teng,Yadong Liu
Developing a diabetic wound dressing that integrates immunomodulation, angiogenesis, and anti-infection effects remains a challenge. Herein, we prepared a novel hydrogen sulfide (H 2 S) donor-modified quaternized chitosan sponge. The sponge enabled controlled H 2 S release in response to reactive oxygen species (ROS), decreasing intracellular ROS while increasing H 2 S levels. The sponge modulated Raw 264.7 macrophage polarization toward the M2 phenotype by inhibiting NF-κB activation, thereby reducing inflammatory cytokine expression and excessive inflammation. The sponge enhanced human umbilical vein endothelial cell migration and angiogenesis by upregulating the vascular endothelial growth factor and endothelial nitric oxide synthase expression. The sponge showed strong antibacterial activity against methicillin-resistant Staphylococcus aureus and Escherichia coli , reducing wound inflammatory responses. The biocompatible sponge accelerated diabetic wound healing by synergistically promoting re-epithelialization, collagen deposition, and angiogenesis, while attenuating inflammation, superior to commercial 3 M™ dressing. Our ROS-responsive H 2 S-releasing cationic chitosan sponge exhibits significant potential for advanced diabetic wound care.
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ACS Applied Polymer Materials
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2026
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IF 5.2
Like Ning,Hanyang Yu,Xinyue Ji,Jian Zhou,Rui Zhang,Chaoqun You
Temozolomide (TMZ) is the first-line chemotherapeutic agent for the most aggressive and lethal form of brain cancer, glioblastoma (GBM). However, the poor aqueous solubility, short plasma half-life, and dose-dependent hematotoxicity severely limited its clinical efficacy. While localized drug delivery systems offer a promising strategy to enhance therapeutic outcomes, their success hinges on precise responsiveness to dynamic tumor microenvironmental cues. In this study, a reactive oxygen species (ROS)-responsive, natural polysaccharide-based hydrogel (TMZ@TCNC/SA) was developed by using nanocellulose and alginate to enable stimuli-triggered delivery of TMZ for localized glioblastoma therapy. By incorporating ROS triggers on the polysaccharide structure, TMZ can be released from the hydrogel in response to a highly oxidative tumor microenvironment. Moreover, released TMZ could induce ROS generation and positively accelerate the TMZ release process, thereby achieving rapid drug accumulation at the tumor site. The hydrogel exhibited H2O2-triggered degradation (96% within 24 h), achieved exceptional TMZ loading (88%) with tumor-specific release (91%, pH 5.5), and reduced viability by 87% and suppressed the invasion by 79% in GBM cells. In vivo experiments demonstrated that the TMZ@TCNC/SA hydrogel had significantly reduced GBM recurrence. These findings suggest that the self-propelling TMZ@TCNC/SA hydrogel is a promising ROS-triggered drug delivery system for efficient GBM inhibition.
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International Journal of Nanomedicine
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2025
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IF 6.5
Shanlei Zhou,Yu Zhang,Eudald Casals,Muling Zeng,Manuel Morales-Ruiz,Qingshi Liu,Bo Zhang,Gregori Casals
Introduction Combining natural antioxidants with nanozymes represents a promising strategy to enhance therapeutic outcomes in oxidative stress-related diseases. This study integrates quercetin (Que), a plant-derived flavonoid with strong antioxidant activity, and cerium oxide nanozymes (CeO2NZs) into mesoporous silica (mSiO2) to enhance therapeutic efficacy and overcome the poor solubility and bioavailability of natural antioxidants.Methods Large-pore mSiO₂ (11 nm) were synthesized via a sol–gel method to encapsulate cerium oxide nanozymes (CeO₂NZs). Que was loaded using solvent impregnation to obtain (CeO₂/Que)@mSiO₂ nanocomposites. Structural and chemical characterization was performed, and biological evaluations were conducted in A549 cells.Results The incorporation of a large mesopore mSiO₂ (11 nm) significantly enhanced Que loading capacity and its sustained release in cell culture media. The (CeO₂/Que)@mSiO₂ nanocomposite demonstrated excellent biocompatibility, effective ROS scavenging, and significant downregulation of inflammatory cytokines (IL-1β, IL-6, TNF-α) compared to free Que.Conclusion The (CeO₂/Que)@mSiO₂ nanoplatform offers synergistic antioxidant and anti-inflammatory effects, supporting its potential for treating oxidative stress-related inflammatory conditions.
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Journal of Materials Chemistry B
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2025
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IF 5.7
Yipiao Zhang,Tian Tian,Zhaokui Zeng,Chuanpin Chen,Rongrong Wang,Suhong Chen,Hongliang Zheng
The treatment of breast cancer (BC) remains a major challenge. Although chemotherapy is currently the most common treatment, it is limited by high side effects. Responsive drug delivery systems (DDS) enable the controlled release of drugs, which can decrease the side effects of chemotherapy and improve efficacy. However, achieving precise delivery and targeted release of drugs is a major challenge. Here, we present ultrasound-triggered reactive oxygen species (ROS)-responsive conjugated polymer nanoparticles for combination therapy of BC. The conjugated polymer nanoparticles are candidates for the development of potential acoustic sensitizers due to their structural properties with good stability and biocompatible acoustic activation properties. In this study, sono-sensitive polymer nanoparticles (SPN) were used for spatiotemporally controlled sonodynamic therapy (SDT) and ROS-responsive chemotherapy. It was demonstrated that the SPN possessed potent acoustic-dynamic properties and could be activated by ultrasound to generate high levels of ROS, which cleaved ROS-responsive junctions, thereby facilitating the release of camptothecin. Furthermore, the SPN exhibited good long circulation properties and biocompatibility in vivo. The SPN combined with ultrasound treatment showed significant therapeutic effects in both BC cell lines and hormonal mouse models, with tumor suppression rates as high as 76.98 ± 9.09%, and no cardiotoxicity or other side effects were observed. Therefore, the present study provides a feasible strategy for designing novel controlled-release drug systems to improve the therapeutic efficacy of BC.
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Acta Biomaterialia
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2025
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IF 9.6
Zhihao Zhao,Ke Ling,Jun Yan,Zhexiang Wang,Chuntao Chen,Dongping Sun,Jian Liu
Calcium ions (Ca²⁺) and reactive oxygen species (ROS) play pivotal roles in cellular signaling and the regulation of diverse biological processes. Complex and dynamic interactions between Ca²⁺ and ROS signaling pathways are often exploited by tumor cells to resist therapeutic interventions. In this study, we present a strategy of cancer treatment based on the reciprocally reinforcing interplay between ROS burst and mitochondrial calcium overload. The major components of our nano carriers integrate CaCO 3 nanoparticles loaded with glucose oxidase (GOx), and copper peroxide nanodots (CPDs) in a DSPE-S-S-PEG-modified liposomal format (abbr. GCCL,). This hybrid nanosystem is designed to facilitate controlled and accelerated release of Ca²⁺ and ROS, thereby establishing dual positive feedback loops that amplify both mitochondrial calcium accumulation and oxidative stress. By harnessing this synergistic cycle, our platform enhances the efficacy of chemodynamic therapy and calcium-induced mitochondrial damage, offering a promising strategy for translational cancer treatment. Statement of significance Here we report a strategy of antitumor therapeutic by designing a dual positive feedback loop of pH-driven self-accelerated Ca 2+ and H 2 O 2 release, thus reciprocally promoting ROS production and mitochondrial calcium overload for tumor eradication. After cellular uptake of GCCL, releasing of the cargos inside the liposomes can introduce a cascade of chemical reactions and biochemical cues, leading to calcium overload and ROS burst. These two major effects are mutually linked with each other, which is utilized by our GCCL design to fuel the positive feedback loops for tumor cell apoptosis in vitro and effective cancer ablation in vivo . Our nano therapy stands out with improved tumor suppression, with a lower dosage of copper element in the treatments of 4T1 xenograft tumor-bearing BALB/c mice model.
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NEUROCHEMISTRY INTERNATIONAL
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2025
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IF 4
Yinpei Huang,Hailun Xie,Lian Liu,Heng Zhao,Bing Li,Feng Zhang
Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (IH), which induces oxidative stress and neuronal apoptosis, ultimately leading to progressive cognitive impairment. This study investigated the neuroprotective potential of a reactive oxygen species (ROS)-responsive nanotherapeutic, namely TPCD nanoparticles (TPCD NP), synthesized through the conjugation of Tempol and phenylboronic acid pinacol ester to β-cyclodextrin, in both in vivo and in vitro models. In rats, intravenous administration of TPCD NP improved memory performance as assessed by the Morris water maze test, and preserved hippocampal neuronal morphology. TPCD NP significantly reduced intracellular ROS content and malondialdehyde (MDA) levels while restoring antioxidant capacity, including superoxide dismutase (SOD) and glutathione (GSH). Apoptosis was attenuated, as evidenced by the downregulation of Bax and cleaved caspase-3, and the upregulation of Bcl-2 expression. Mechanistically, TPCD NP enhanced the nuclear translocation of nuclear factor erythroid 2–related factor 2 (NRF2), suppressed Kelch-like ECH-associated protein 1 (KEAP1), and increased heme oxygenase-1 (HO-1) expression. The protective effects were abolished by ML385, a selective NRF2 inhibitor, confirming the essential role of NRF2 activation in mediating the antioxidant and anti-apoptotic effects of TPCD NP. In conclusion, TPCD NP attenuates oxidative stress and apoptosis induced by IH in the hippocampus by activating the NRF2/KEAP1/HO-1 pathway. These findings highlight TPCD NP as a promising therapeutic strategy for OSA-associated neurodegeneration.
研究领域:
医学
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神经科学
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药理学
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Small
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2025
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IF 12.1
Xiangyu Zhang,Yujie Zhu,Zijian Xiong,Wenjie Xie,Ming Shao,Zhuang Liu
Inflammatory bowel disease (IBD) such as ulcerative colitis (UC) is an autoimmune disease characterized by persistent inflammation along the gastrointestinal tract with excessive generation of reactive oxygen species (ROS)/reactive nitrogen species (RNS) generation. Here, catalase (CAT)-containing microreactor capsules with long-lasting broad-spectrum ROS/RNS-scavenging capability are developed for the treatment of IBD. In this design, CAT is encapsulated in the dense hydrogel network of calcium alginate (ALG) microspheres, which provides long-term protection of CAT activity in protease-rich intestinal environment. Afterward, the polydopamine (PDA) modification on the surface of CAT@ALG microspheres can provide them bioadhesiveness to achieve prolonged retention in the intestinal tract and broad-spectrum scavenging capability against various types of ROS/RNS beyond hydrogen peroxide. Enteric capsules are further used to protect the CAT@ALG–PDA microspheres from gastric fluid for selective release at the intestinal site. The combined action of PDA and CAT in CAT@ALG–PDA microreactors results in the broad-spectrum scavenging of excess ROS/RNS and regulates redox balance in acute UC rat model, showing satisfactory therapeutic effects superior to the mesalazine and adalimumab at clinically relevant doses without obvious side effects. This work highlights that these CAT@ALG–PDA capsules can act as long-acting broad-spectrum ROS/RNS reactors, promising for IBD treatment.
研究领域:
医学
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生物材料学
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药剂学
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