RSC Advances
·
2026
·Vol. 16
·期 43
·
IF 6.1
Weikai Zhang,Yating Fan,Zhangjin Qin,Wei Chen,Hewei Zhang,Fuchao Mao,Quanzhong Yang,Shuang Li,Chongkai Zhai
Diabetic chronic wounds remain a leading cause of non-traumatic lower-extremity amputation, driven by four concurrent pathological processes: multidrug-resistant bacterial infection, excessive reactive oxygen species (ROS), sustained pro-inflammatory macrophage polarization, and impaired neovascularization. Conventional wound dressings address only one or two of these processes, and no single-target approach can interrupt this self-reinforcing pathological network. To address this limitation, we designed TAZNP/ADH-OHA Gel, a ROS/pH dual-responsive composite hydrogel dressing. Mesoporous silica nanoparticles (MSNs) were co-loaded with the antimicrobial peptide Pexiganan (AMP, EE% = 90.10%) and Zn 2+ (EE% = 33.71%), then coated with a tannic acid-Zn 2+ metal-phenolic network (TA-Zn 2+ MPN) to form TAZNP nanoparticles, which were subsequently embedded in a dynamically crosslinked ADH-HA/OHA hydrazone hydrogel matrix. The resulting scaffold exhibited interconnected macroporosity, stable viscoelastic properties ( G ' > G ″, 0.1-10 Hz), a yield strain of ∼175%, tissue adhesion of 3.97 kPa, and an equilibrium swelling ratio of 250-300%. Cumulative AMP release increased from 69.10% under physiological conditions (pH 7.4) to 94.93% under combined diabetic wound conditions (pH 6.0 + 10 mM H 2 O 2 + 25 mM glucose), with Zn 2+ reaching 86.41% under identical conditions. Early-stage kinetic analysis further demonstrated highly synchronized AMP/Zn 2+ release, with apparent release-rate ratios ranging from 1.05 to 1.22 across the tested microenvironments. In vitro assays demonstrated effective antibacterial and anti-biofilm activity against S. aureus and E. coli , with TAZNP/ADH-OHA Gel outperforming free TAZNP and ADH-OHA Gel alone. The composite hydrogel protected HSFs and HUVECs against high-glucose cytotoxicity, restored HSF wound closure from 37.44% to 70.79%, and rescued HUVEC tube formation, restoring total tube length from 5615.88 µm to 15 486.40 µm and number of segments from 26.68 to 249.33. In LPS-stimulated RAW264.7 macrophages, iNOS and TNF-α mRNA were reduced to 0.59-fold and 0.61-fold, while Arg-1 and IL-10 were elevated to 4.13-fold and 5.12-fold. Flow cytometry confirmed genuine M1-to-M2 phenotypic switching, with the M1 proportion reduced from 60.61% to 25.92% and the M2 proportion increased from 35.11% to 75.44%. These results demonstrate that TAZNP/ADH-OHA Gel integrates microenvironment-responsive synchronized co-delivery with antibacterial, antioxidant, pro-angiogenic, and immunomodulatory activities, providing a promising multifunctional platform for diabetic wound management.
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高影响因子
Pharmaceutics
·
2026
·Vol. 18
·期 3
·323
·
IF 6.9
Xiao Yang,Hui Wang,Wenjuan Zhang,Peng Gao,Xudong Yu,Weijia Qing,Ping Deng,Jingdian Li,Yan Luo,Li Tian,Jia Xie,Mengyan Chen,Zhengping Yu,Huifeng Pi,Ting Liu,Shenglin Luo
Background/Objectives: High-voltage, low-current electric shocks inflict superficial second-degree burns on the skin, accompanied by a vicious cycle of excessive oxidative stress and inflammation. As efficient treatment of such electrical burns remains a clinical challenge, we explored the efficacy of an injectable thermosensitive chitosan hydrogel engineered with an antioxidant agent (astaxanthin) and an anti-inflammatory agent (ibuprofen) for the treatment of high-voltage, low-current electrical burn injuries.Methods: The proposed CS/AST/IBU hydrogel was prepared and its thermosensitivity was characterized. Subsequently, the hydrogel was injected into the wounds of male Sprague–Dawley (SD) rats subjected to electrical burn injury (20 kV, 3 mA). Finally, a series of experiments were performed to elucidate the dynamics of wound healing and the mechanisms by which the hydrogel promotes wound repair.Results: The injectable hydrogel, through its thermally responsive gelation effect at 37 °C, adapts to the complex irregularities of the wound surface. This facilitates the release of astaxanthin and ibuprofen throughout the wound, which collectively diminish the formation of reactive oxygen species and MDA. Furthermore, it enhances the synthesis of endogenous antioxidants such as SOD, CAT, and GSH; encourages collagen deposition; stimulates the development of dermal appendages; and fosters neovascularization. It interrupts the deleterious cycle of oxidative stress and inflammation mediated by the NF-κB signaling pathway, thereby suppressing the expression of pro-inflammatory markers such as TNF-α, CD11b, and IL-1β while upregulating CD163, an anti-inflammatory receptor.Conclusions: The use of this multipronged, contour-adaptive hydrogel represents an effective strategy for complex wound management and demonstrates broad therapeutic potential for superficial second-degree electrical burns caused by high-voltage, low-current discharge.
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APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2026
·
IF 3.5
Li Tong,Li Ning,Li Yi,Liu Jinwen,Hao Dajie
Oxidative stress and inflammasome-driven inflammation are key contributors to atherosclerotic disease progression. Here, we report a ROS-responsive hyaluronic acid-PEGDA hydrogel designed for the sustained delivery of palmitoleic acid. In the study, catechol-functionalized hyaluronic acid was cross-linked with polyethylene glycol diacrylate to create an extracellular matrix mimic that possessed tunable mechanical strength and redox-sensitive degradability. It showed controlled release of palmitoleic acid under normal physiological conditions and a faster rate of release under oxidative conditions. In vitro studies using vascular endothelial cells and macrophages demonstrated good cytocompatibility and a marked reduction in intracellular reactive oxygen species, lipid peroxidation, and pro-inflammatory cytokine secretion. At the molecular level, treatment with the palmitoleic acid-loaded hydrogel resulted in activation of AMP-activated protein kinase, inhibition of NF-κB nuclear translocation, and suppression of NLRP3 inflammasome activation, as evidenced by decreased caspase-1 cleavage and IL-1β maturation. These findings indicate that ROS-responsive hydrogel-mediated delivery of palmitoleic acid effectively modulates oxidative and inflammatory signalling pathways relevant to atherosclerosis. Graphical
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Advanced Healthcare Materials
·
2026
·
IF 11
Min Liu,Shuya Wang,Ruishi Li,Weimin Qi,Tingli Xiong,Xiaojing Shi,Wensheng Chen,Feixiang Ding,Chenglong Wei,Junyan Liu,Niansheng Li,Qiong Huang,Zhaoqian Liu,Kelong Ai
Acute liver injury (ALI) is a significant clinical cause of liver failure, potentially occurring at any stage of liver disease and posing a considerable health burden. One prevalent model of ALI stems from acetaminophen (APAP) overdose, where a vicious cycle of “mitochondrial damage-inflammation amplification” and limited availability of small molecular drugs hinder current therapeutic approaches. Herein, a novel tannic acid (TA)-strontium (Sr) nanodrug (SrTA) is proposed. With liver-accumulating and mitochondria-targeting capabilities, SrTA effectively harnesses the broad-spectrum antioxidant properties of TA along with the calcium homeostasis-regulating function of Sr 2+ . And its therapeutic efficacy surpassed that of an equivalent dose of N-acetylcysteine (NAC). Mechanistically, SrTA directly scavenges mitochondrial reactive oxygen species (ROS), protects mitochondrial integrity, and alleviates endoplasmic reticulum (ER) stress and intracellular oxidative damage. Additionally, SrTA antagonizes calcium signaling, reduces the formation of mitochondria-ER contacts, and inhibits mitochondrial calcium overload. By safeguarding mitochondrial function and preventing the aberrant opening of the mitochondrial permeability transition pore (mPTP), SrTA significantly curtail hepatocyte death and mitigates mtDNA-induced sterile inflammation, effectively halting the injury cascade. In conclusion, this study presents a novel therapeutic strategy for ALI that targets mitochondria and synergistically regulates ROS bursts and calcium overload, achieving multifaceted therapeutic effects.
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高影响因子
Small
·
2025
·
IF 12.1
Ruru Xiong,Min Zhou,Huishuang Li,Lijuan Wang,Guixia Ling,Peng Zhang
Due to hypoxia, excessive reactive oxygen species (ROS), dense bacterial biofilms, and complex inflammatory microenvironment, chronic diabetic wound healing presents a huge challenge. Currently, sustainable treatments for this multifaceted problem have not been found. Here, microalgae and silver (Ag)─fulvic acid (FA) NPs are used to develop a multinetwork hydrogel (C@Ag─KGCM) based on oxidized konjac glucomannan (OKG) for the treatment of diabetic chronic wound (DCW). The lower hydrogel carries microrobots of Chlamydomonas rheinhardtii (C. rheinhardtii) , which continuously release bio-oxygen under light irradiation to alleviate hypoxia in deep wound tissues. The upper layer carries Ag─FA NPs formed by Ag + and FA self-assembly chelation complex, which can effectively inhibit bacterial growth and remove bacterial biofilms through photothermal-therapy-based Near - Infrared (NIR) 808 nm. C. reinhardtii and Ag─FA NPs synergistically scavenge excessive ROS. Therefore, a new concept of “three-pronged strategies” that addresses multiple problems in the wound microenvironment of diabetic patients has been proposed. Histological analysis of wound tissues shows that the C@Ag─KGCM bilayer hydrogel can promote chronic diabetic wound healing and tissue regeneration, indicating promising potential for its treatment of DCW healing.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Ye-Fei Ruan,Jin-Hui Wang,Wen-Da Zhong,Lin Qiu
Targeting mitochondrial dysfunction in inflamed lung vessels addresses a key challenge in acute lung injury treatment, where current therapies lack precision and efficacy. • We develop smart nanoparticles that actively seek out injured blood vessels and release medicine only where oxidative stress is high, enabling enhanced mitochondrial repair. • This strategy markedly improves lung function and survival in mice with acute lung injury, demonstrating a promising approach for treating severe pulmonary inflammation. Acute lung injury (ALI) is a life-threatening condition with complex pathogenesis. Mitochondrial dysfunction in pulmonary vascular endothelial cells serves as a central hub, driving oxidative stress, inflammation, and barrier disruption. Existing treatments are limited by poor targeting and insufficient efficacy. To address this, we engineered a novel dual-targeting nanoplatform, P-selectin-directed and ROS-responsive fucoidan micelles loaded with the mitochondrial modulator Mitochonic Acid 5 (Fuc-TP@MA-5). Here we show that this system actively homes to inflamed lung endothelium via fucoidan-P-selectin binding and selectively releases MA-5 within the high-ROS microenvironment via thioketal linker cleavage. This enhanced delivery potently restores mitochondrial membrane potential and ATP production, scavenges excess ROS, and inhibits endothelial apoptosis. Consequently, Fuc-TP@MA-5 significantly attenuates pulmonary edema, vascular hyperpermeability, and inflammatory cytokine storm in a murine model of LPS-induced ALI, outperforming free MA-5. Our work establishes a targeted mitochondrial functional improvement strategy, offering a promising and intelligent nanotherapeutic paradigm for treating ALI and other vascular inflammatory disorders. Download: Download high-res image (166KB) Download: Download full-size image
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Pingchuan Wang,Tianming Li,Changping Niu,Siyu Sun,Dongyan Liu
Reactive oxygen species (ROS) damage to the intestinal barrier is a side effect of prolonged hyperoxia therapy in neonates, which impairs growth and development of the intestine and promotes intestinal diseases. However, the research on clinical prevention and treatment is lacking. Therefore, we investigated the molecular mechanisms of the neonate intestinal response against hyperoxia-derived ROS to find targets for intestinal barrier damage prevention. Human intestinal epithelial cells were incubated under hyperoxia (85% oxygen) to build an in vitro model. ROS and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway were inhibited to detect the MAPK/ERK pathway, nuclear factor erythroid factor 2-related factor 2 (Nrf2), hypoxia-inducible factor-1α (Hif-1α), and interleukin-17D (IL-17D) expression. Nrf2 was inhibited to detect Hif-1α and IL-17D expression. Hif-1α was inhibited to detect Nrf2, IL-17D, and tight junction proteins expression and apoptosis. Cells were treated with human recombinant IL-17D to detect TNF-α, IL-1β, IL-10, and tight junction proteins expression. ROS, Nrf2, Hif-1α, and IL-17D were upregulated and the MAPK/ERK pathway was activated under hyperoxia. But ROS inhibition downregulated the MAPK/ERK pathway, Nrf2, Hif-1α, and IL-17D. MAPK/ERK pathway inhibition downregulated Nrf2, Hif-1α, and IL-17D. Nrf2 inhibition downregulated Hif-1α and IL-17D. Hif-1α inhibition downregulated Nrf2, IL-17D, tight junction proteins, and exacerbated apoptosis. The recombinant IL-17D downregulated TNF-α, IL-1β, but upregulated IL-10 and tight junction proteins. We concluded that Hyperoxia-generated ROS activated the MAPK/ERK pathway to regulate Nrf2, Hif-1α, and IL-17D expression. Nrf2 and Hif-1α were interdependent and promoted IL-17D. Importantly, Hif-1α and IL-17D expression protected the intestinal epithelial barrier.
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高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Hong Zhu,Jie Xu,Min Zhao,Hangqi Luo,Minjie Lin,Yuting Luo,Yuan Li,Huacheng He,Jiang Wu
As conventional treatments for diabetic wounds often fail to achieve rapid satisfactory healing, the development of effective strategies to accelerate diabetic wound repair is highly demanded. Herein, fibroblast growth factor 21 (FGF21) and metformin co-loaded multifunctional polyvinyl alcohol (PVA) hydrogel were fabricated for improved diabetic wound healing. The in vitro results proved that the hydrogel was adhesive and injectable, and that it could particularly scavenge reactive oxygen species (ROSs), while the in vivo data demonstrated that the hydrogel could promote angiogenesis by recruiting endothelial progenitor cells (EPCs) through upregulation of Ang-1. Both ROSs’ removal and EPCs’ recruitment finally resulted in enhanced diabetic wound healing. This work opens a strategy approach to diabetic wound management by combining biological macromolecules and small chemical molecules together using one promising environmental modulating drug delivery system.
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Nanomedicine-Nanotechnology Biology and Medicine
·
2021
·
IF 6.458
Haiting Xu,Ruifeng Luo,Lingling Dong,Xiulan Pu,Qiyan Chen,Naijing Ye,Shanshan Qi,Xiaoqin Han,Wenbiao Nie,Chaomei Fu,Yichen Hu,Jinming Zhang,Fei Gao
An oral nanoparticle (NPs) encapsulated in chitosan/alginate hydrogel (CA-Gel) with dual-sensitive in pH and reactive oxygen species (ROS) was developed to load curcumin (CUR) based on the intracellular-specific characteristics of macrophages. Chondroitin sulfate (CS) wrapped PBAE-SA-PAPE with intracellular pH/ROS dual-sensitive characteristics and CUR via a simple nanoprecipitation method to form NPs (CS-CUR-NPs), and mixed CA-Gel to acquire the final preparation (CS-CUR-NPs-Gel). CS-CUR-NPs displayed an ideal average particle size (179.19 ± 5.61 nm) and high encapsulating efficiency (94.74 ± 1.15%). CS showed a good targeting ability on macrophages and the CA-Gel contribution in protecting NPs from being destroyed in the upper gastrointestinal tract . As expected, CS-CUR-NPs-Gel could significantly alleviate inflammation in DSS-induced UC mice via TLR4-MAPK/NF-κB pathway. This study is the first to attempt to design a novel pH/ROS dual-stimulated release strategy in helping intracellular CUR delivery and anticipated for efficient anti-UC therapy.
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高影响因子
Biomedical Materials
·
2021
·Vol. 16
·期 6
·064101
·
IF 3.715
Xinyu Wu,Jie Ding,Peifang Xu,Xue Feng,Zhaoyi Wang,Tong Zhou,Chenxi Tu,Wangbei Cao,Jieqi Xie,Liwen Deng,Liyin Shen,Yang Zhu,Zhongru Gou,Changyou Gao
The modulation of inflammation in tissue microenvironment takes an important role in cartilage repair and regeneration. In this study, a novel hybrid scaffold was designed and fabricated by filling a reactive oxygen species (ROS)-scavenging hydrogel (RS Gel) into a radially oriented poly(lactide-co-glycolide) (PLGA) scaffold. The radially oriented PLGA scaffolds were fabricated through a temperature gradient-guided phase separation and freeze-drying method. The RS Gel was formed by crosslinking the mixture of ROS-responsive hyperbranched polymers and biocompatible methacrylated hyaluronic acid (HA-MA). The hybrid scaffolds exhibited a proper compressive modulus, good ROS-scavenging capability, and cell compatibility. In vivo tests showed that the hybrid scaffolds significantly regulated inflammation and promoted regeneration of hyaline cartilage after they were implanted into full-thickness cartilage defects in rabbits for 12 w. In comparison with the PLGA scaffolds, the neo-cartilage in the hybrid scaffolds group possessed more deposition of glycosaminoglycans and collagen type II, and were well integrated with the surrounding tissue.
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CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Jiayu Xiao,Luo Hai,Ke Yang,Yuze Luo,Zefeng Wang,Junqin Li,Chunlei Ou,Li Wang,Le Deng,Dinggeng He
Reactive oxygen species (ROS) such as hydroxyl radicals ( OH) and singlet oxygen ( 1 O 2 ) have emerged as promising therapeutic agents for combating biofilm-associated bacterial infections. However, the hypoxic microenvironments in the biofilms severely hinder the ROS production. Herein, we have rationally integrated copper peroxide (CP) and indocyanine green (ICG) into a polydopamine (PDA) nanoparticle to construct a versatile hybrid nanoplatform (PDA/CP/ICG), which can enhance ROS generation for highly efficient biofilm elimination by relieving hypoxic microenvironment. When the PDA/CP/ICG accumulates at the infection site or biofilm, the acidic microenvironment triggers the co-release of Cu 2+ and H 2 O 2 , and the former can catalyze the conversion of self-supplied H 2 O 2 into OH via a Fenton-like reaction and consume the overexpressed antioxidant glutathione (GSH) to further promote the oxidative stress. Moreover, with the help of an 808 nm laser, the hyperpyrexia caused by PDA induces the decomposition of CP into O 2 that is immediately converted by ICG into 1 O 2 . The PDA/CP/ICG shows satisfactory antibacterial and antibiofilm effect due to the self-amplified production of OH and 1 O 2 , and outstanding wound healing with good in vivo biosafety. Overall, this study provides a facile paradigm in ROS-based biofilm elimination, and the proposed hypoxia-irrelevant bactericidal nanoplatform has great potential for future biomedical applications.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xiangyu Huang,Zucheng Shen,Qi Deng,Chengfei Zhao,Xiaofeng Cai,Shaoteng Huang,Mingbo Zhang,Yanzhuo Lv,Dongliang Yang,Junyang Zhuang,Ning Li
Diabetic foot ulcers (DFU) infections have been a major setback in wound healing, yet there is no effective therapeutic intervention. Here we report a nano-multidrug co-delivery system based on arginine-terminal butterfly-shaped peptide dendrimers (C&D@Z) that effectively kill bacteria and promote wound healing. Firstly, upon the near-infrared light irradiation, reactive oxygen species (ROS) was generated from the loaded photosensitizers, and then mediated bacteria killing. Next, the excessive ROS reacted with the designed butterfly-shaped dendrimers to generate sustained and abundant nitric oxide (NO), which exerted bactericidal action, as well as produced anti-inflammatory and angiogenesis effects. The co-delivery system, facilitated by the generation of NO, penetrated deeply into the biofilm, thereby effectively eliminating bacteria. The enhanced bactericidal and healing efficiency was investigated through biofilm penetration and wound healing experiments. Collectively, our system leveraged the highly-branched and cavity structures of the butterfly peptide dendrimer to realize the tight contact between the arginine groups and photosensitizer to achieve efficient conversion from ROS to NO, and the C&D@Z exhibited superior NO production, optimal photodynamic therapy utilization and effective penetration performance through cascade reaction between photodynamic therapy and NO therapy, may serve as a promising therapeutic approach for DFU infections.
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