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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Advanced Healthcare Materials
·
2026
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IF 11
Zhiwen Wang,Yue Xie,Jiahui Zhang,Min Yang,Zhiyue Zou,Chun Zhang
Acute kidney injury (AKI) and chronic kidney disease (CKD), despite distinct etiologies, share a common pathological axis characterized by reactive oxygen species (ROS) burst, ferroptosis activation, and sustained inflammation. Targeting this ROS–ferroptosis–inflammation cycle represents a promising therapeutic strategy; however, current nanoplatforms are limited by insufficient responsiveness and limited capacity to regulate shared pathological mechanisms across distinct renal disease models. Here, we develop an engineered ROS-responsive nanozyme by integrating diselenide-bridged organosilica, hyaluronic acid (HA)-modified cerium oxide (CeO 2 ), and a selenium-containing diselenide framework. Under oxidative stress, MON@HA-CeO 2 undergoes ROS-triggered disassembly, coupling HA-CeO 2 -mediated ROS scavenging with selenium-related GPX4 restoration to suppress lipid peroxidation, ferroptosis, and inflammatory amplification. In both glycerol-induced AKI and unilateral ureteral obstruction (UUO)-induced renal fibrosis models, the nanozyme significantly improves renal function and attenuates tissue injury, fibrosis, and inflammation. Overall, this work demonstrates a versatile strategy for targeting a shared pathological axis and provides a promising platform for the treatment of diverse renal diseases.
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Frontiers in Pediatrics
·
2026
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IF 2.2
Yingying Jing,Gaofeng Xian,Gang Wu,Lingna Ye,Hanshu Wang,Xiaoni Cai
IntroductionThere is a clinical contradiction between postoperative analgesia and gastrointestinal functional recovery following intestinal ischemia-reperfusion (I/R) injury.MethodsIn this study, a reactive oxygen species (ROS)-responsive nanoplatform (LA-CLX-NP) was constructed by conjugating DSPE-PEG with α-lipoic acid (LA) followed by self-assembly and encapsulation of celecoxib.ResultsThe nanoparticles exhibited uniform size, good stability, and ROS/pH dual-responsive drug release properties. In vitro, LA-CLX-NP was efficiently internalized by macrophages and, compared with free drugs, more effectively scavenged ROS, restored redox balance, and modulated inflammatory cytokines. In a mouse model of intestinal I/R injury, LA-CLX-NP significantly reduced diarrhea incidence, increased mechanical withdrawal threshold, decreased abdominal licking and scratching behaviors, preserved ZO-1 tight junctions, suppressed COX-2 overexpression, and normalized serum cytokine profiles, with superior efficacy to single agents.DiscussionThis strategy achieves on-demand delivery of celecoxib to the inflamed intestine, exerts synergistic anti-inflammatory and antioxidant effects, and thereby reconciles effective pain relief with rapid gastrointestinal recovery, offering a new approach for postoperative management of intestinal I/R injury.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
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IF 5.9
I-Chen Tsai,Luhui Cai,Cheng Tian,Zihan Ni,Wenqian Ding,Yue Li,Weichang Li,Qiong Xu
A ROS-responsive injectable hydrogel for DMI delivery is developed. • DMI suppresses inflammation and oxidative stress in DPSCs. • DMI does not directly promote odontogenesis under inflammation. • DMI restores odontogenesis via macrophage-mediated modulation. • The hydrogel enhances reparative dentin formation in vivo . Pulpitis is a common inflammatory disease of the dental pulp in which excessive inflammation and oxidative stress severely compromise the regenerative capacity of dental pulp stem cells (DPSCs), posing a major challenge for successful vital pulp therapy. Herein, we report an immunometabolic strategy that combines dimethyl itaconate (DMI) with a reactive oxygen species (ROS)-responsive injectable hydrogel to modulate the inflammatory microenvironment and promote functional pulp regeneration. We demonstrated that DMI effectively suppressed lipopolysaccharide (LPS)-induced inflammatory cytokine expression and ROS accumulation in DPSCs. Notably, DMI did not directly enhance odontogenic differentiation under inflammatory conditions; instead, it indirectly restored the odontogenic potential of DPSCs by attenuating macrophage-mediated inflammation. To enable localized and sustained delivery of DMI, a dual-crosslinked SADA/CMBA hydrogel was developed based on dynamic boronic ester bonds and ionic coordination, allowing ROS-triggered drug release while maintaining structural integrity and biocompatibility. In vitro studies confirmed the hydrogel’s favorable cytocompatibility, anti-inflammatory and antioxidant effects. Furthermore, in an LPS-induced rat pulpitis model, the DMI-loaded hydrogel significantly reduced pulpal inflammation and facilitated reparative dentin formation at the pulp exposure site. Collectively, this study introduces an immunometabolic and microenvironment-responsive therapeutic design for pulpitis treatment and highlights the potential of ROS-adaptive biomaterials to enhance the outcomes of vital pulp therapy. Download: Download high-res image (130KB) Download: Download full-size image DMI@SADA/CMBA hydrogel application for treating pulpitis
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ACS Applied Materials & Interfaces
·
2026
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IF 7.8
Yan Shi,Jinrui Li,Jiaxuan Zhao,Lu Liu,Ruimin Zhan,Dandan Jing,Xiaoya Wang,Dongwei Ma,Junmin Lee,Zhiguo Wang,Ming Kong
Pathological scars are fibrotic disorders arising from aberrant wound healing. PDT is effective but limited by a dense matrix, hypoxia, and post-PDT excessive ROS-induced secondary inflammation. To address this, a NIR-switchable ROS-regulatory liposome (ICC@Lip) with CaO2 NPs (oxygenation to strengthen PDT) and Cu5.4O nanozymes (ROS scavenging) was developed. In addition, inspired by Cyperaceae stems and triangular arrows, a highly penetrable biomimetic microneedle platform loaded with ICC@Lip and collagenase I (ICC@Lip/HPMN) was constructed to realize efficient transdermal cargo delivery and diffusion into a rigid pathological scar matrix. The puncture resistance of ICC@Lip/HPMN was only 56.4% that of conventional rectangular pyramid microneedles, with an effective puncture rate of 96% in mouse skin. In vitro, under NIR irradiation-mediated PDT/PTT, ICC@Lip significantly alleviated intracellular hypoxia and related fibrotic indicators, achieving a cytotoxicity rate of 93.71% against myofibroblasts─1.49-fold higher than that of the IR808 alone group (62.74%)─while reducing M2 macrophage polarization and TGF-β secretion. Notably, timely post-PDT ROS clearance decreased M1 polarization of macrophages and reduced the release of over 50% of inflammatory cytokines. In rabbit ear, a hypertrophic scar model exhibited that ICC@Lip/HPMN reduced the scar elevation index from 3 to 1.7, significantly alleviating collagen deposition and inflammation. The antifibrotic efficacies were majorly exerted through cross-downregulation of TGF-β, IL-4, and toll-like receptor signaling pathways. This study provided a promising adaptive therapeutic strategy of self-strengthened PDT coupling ROS precise regulation for pathological scars.
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Acta Pharmaceutica Sinica B
·
2026
·
IF 14.6
Xinyu Tan,Man Li,Zhibin Lan,Wenxiang Zhang,Junjie Zou,Yibo An,Jingwen Zheng,Xuwen Xiang,Jing Lin,Sheng Lin,Wenjie Ni,Lin Che,Gang Liu,Jing Chen,Zhixiang Lu
To address the intertwined pathologies of oxidative stress, immune dysregulation, and lipid metabolic disorders in acute liver injury (ALI), we engineered an innovative nanosystem: M2@SAM-F21. M2@SAM-F21 features an M2 macrophage membrane coating encapsulating diselenide-bridged mesoporous silica nanoparticles for silymarin and FGF21 plasmid DNA codelivery, enabling synergistic multidimensional treatment. First, reactive oxygen species (ROS)-responsive oxidative stress is mitigated. Diselenide bonds undergo ROS-triggered cleavage, achieving precise silymarin release that efficiently scavenges multiple ROS types, significantly mitigating hepatic oxidative damage. Simultaneously, FGF21 drives immune reprogramming. Efficiently expressed FGF21 protein drives macrophage polarization toward the M2 anti-inflammatory phenotype, effectively reducing proinflammatory cytokine levels, with TNF- α decreased to 61 pg/mL and IL-6 reduced to 20 pg/mL, while increasing IL-10 to 68 pg/mL to reverse the immune microenvironment imbalance. In addition, metabolic homeostasis is restored. Activated fatty acid oxidation pathways substantially decrease serum concentrations of total cholesterol (TC) to 4.984 mmol/L and triglycerides (TG) to 0.586 mmol/L, and almost reduce hepatocellular lipid droplet accumulation by 76%, resolving metabolic dysregulation. In both alcoholic and drug-induced ALI models, M2@SAM-F21 demonstrates exceptional hepatoprotection. For example, it significantly restores serum alanine aminotransferase (ALT) to 46.6 U/L and aminotransferase (AST) to 180 U/L in the alcoholic ALI model, while markedly alleviating histopathological vacuolization and steatosis, with biological distribution imaging confirming inflammation-targeted accumulation and proteomic analysis further elucidating therapeutic mechanisms. Exhibiting superior biosafety and dual therapeutic-prophylactic potential, this system serves as a pioneering paradigm that integrates targeted delivery, intelligent release, and multipathway synergy for ALI treatment.
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Advanced Healthcare Materials
·
2026
·
IF 11
Yang Chen,Li Zhu,Wei Xu,Qi Chen,Fei Teng,Kaiwen Bao,Lu Zhang,Yuan Wang,Wei Wu,Zhiqiang Wang
Esophageal cancer (EC) remains a highly aggressive malignancy with limited therapeutic options and poor prognosis. To address the shortcomings of conventional therapies, we developed a biomimetic, reactive oxygen species (ROS)-responsive nanoprodrug for synergistic photothermal–chemotherapy of EC. Tannic acid and ellagic acid were chemically linked via boronate ester bonds to form a polyphenol-based nanoparticle (TPE). The epidermal growth factor receptor (EGFR)-targeting peptide GE11 was subsequently introduced onto red blood cell membranes (RBCM) to obtain GE11-RBCM, which was then used to cloak the TPE nanoparticles, yielding GE11-RBCM@TPE. The resulting nanoplatform exhibited excellent photothermal conversion capability under near-infrared irradiation and selectively released the therapeutic payload in response to elevated ROS levels within the tumor microenvironment. In vitro studies showed enhanced cellular uptake in EGFR-overexpressing EC cells and markedly increased cell death following combined photothermal and chemotherapeutic treatment. In vivo, GE11-RBCM@TPE significantly inhibited tumor growth with negligible systemic toxicity and prolonged blood circulation. Transcriptomic analysis further revealed up-regulation of pro-apoptotic ( PER1 , HK2 , BMF , DAPK2 ) and autophagy-related genes ( ATP6V0D2 , HDAC10 , BNIP3 , DEPP1 , ATG9B , NAT16 ), while SQSTM1 and IL6 were down-regulated, indicating simultaneous activation of apoptosis and autophagy. These findings suggest that GE11-RBCM@TPE represents a promising strategy for precise and effective treatment of esophageal cancer.
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JOURNAL OF CONTROLLED RELEASE
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2026
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IF 12.4
Yanyan Wang,Kaishun Qi,Youyou Li,Ruirui Wei,Yuanda Lou,Min Liu,Shengjiang Wei,Yajie Zhao,Jianping Liu,Hongliang He,Wenli Zhang
Oxidative stress and macrophage autophagy dysfunction jointly drive plaque vulnerability and rupture, ultimately leading to acute atherothrombotic cardiovascular events. However, current monotherapies based solely on antioxidant intervention or autophagy induction remain insufficient for effective atherosclerosis management. Here, we reported the development of a cationic antioxidant dextran derivative (DKT) with intrinsic reactive oxygen species (ROS)-scavenging capacity, designed to co-deliver rapamycin-loaded reconstituted high-density lipoprotein (RC-rHDL) for synergistic atherosclerosis therapy. Through electrostatic interactions, DKT mediated the assembly of small-sized RC-rHDL into large-sized nanoassemblies (RT-rHDL), enabling efficient vascular targeting and ROS-triggered disassembly within plaques. In vitro studies demonstrated that RT-rHDL nanoassemblies effectively inhibited foam cell formation, suppressed inflammation, and reduced apoptosis by combining ROS elimination with autophagy activation. In vivo, RT-rHDL nanoassemblies accumulated at atherosclerotic lesions via endothelial binding and penetrated deeply into foam cell–rich plaques. A three-month intravenous treatment in apoE −/− mice significantly reduced plaque size, minimized necrotic core areas, resolved local inflammation, and enhanced plaque stability. Mechanistic investigations confirmed that systemic and lesional oxidative stress attenuation together with macrophage autophagy restoration underpinned these therapeutic benefits. Collectively, our findings highlight the importance of simultaneously modulating cellular functions and the plaque microenvironment, offering a novel synergistic nanotherapeutic strategy for atherosclerosis treatment.
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Biomaterials Advances
·
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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Antioxidants
·
2026
·Vol. 15
·期 6
·722
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IF 8.2
Quan Zhu,Yangyang Zhang,Xinyi Zhu,Huijuan Zhang,Chuyu Xiao,Yingying Yang,Ting Huang,Jun Lu,Chang Liu,Chunjing Chen,Yueyuan Zhou,Tao Liu,Biyuan Liu,Fangguo Lu
Ferroptosis and cuproptosis are promising anti-tumor treatment strategies. Elesclomol (ES) is a kind of common cuproptosis inducer, and cisplatin (DDP) is a commonly used drug in liver cancer chemotherapy, which can induce cells to undergo ferroptosis. Both of these cell death processes require inducing cells to generate oxidative stress. Therefore, elesclomol and cisplatin may have a synergistic effect in anti-tumor treatment. Here, we designed an active oxygen-responsive nano-delivery system and conducted in vitro and in vivo to study the synergistic anti-liver cancer effect of elesclomol and cisplatin. Our data showed that the elesclomol nanoparticles can effectively inhibit the growth of liver cancer cells and showed extremely low organ toxicity. Elesclomol exhibited a synergistic effect with cisplatin in vitro, but the combined treatment of the two did not outperform single drug treatment in vivo. The reason might be that the nuclear factor erythroid 2-related factor 2 (Nrf2) protein in liver cancer cells is feedback-expressed, inhibiting the oxidative stress effects induced by elesclomol and cisplatin. Therefore, this study provides reference data for exploring the mechanism of elesclomol’s synergistic anti-liver cancer treatment with cisplatin and offers a feasible strategy for future precise liver cancer treatment and improving chemotherapy efficacy.
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International Journal of Nanomedicine
·
2026
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IF 8.7
Jiaqi Li,Zheng Zhong,Yuhe Tan,Xiaohong Ma,Ruohong Wang,Guoyao Gao,Xian Zhang,Ziqing Zhou,Yin Zhao,Jia Liu,Xufang Sun
Background The multifaceted pathogenesis of diabetic retinopathy (DR) involves numerous pathways, among which oxidative stress and Rho-associated kinase (ROCK) signaling are critically implicated. The failure of current anti-VEGF monotherapies to address these key pathological processes limits their efficacy. While the ROCK inhibitor Fasudil is a promising candidate, its clinical translation for DR is hindered by poor ocular retention and lack of target specificity.Methods We engineered a reactive oxygen species (ROS)- and pH-dual responsive polydopamine nanoplatform (Fasudil@PDA) to deliver Fasudil while concurrently scavenging oxidative stressors.Results The Fasudil@PDA nanoparticles achieved a high drug loading capacity of ~28%. The release kinetics were specifically engineered to be responsive to the DR microenvironment. Under high ROS conditions in vitro, the platform demonstrated a sustained and efficient release profile, achieving a cumulative release of 87.3% over 56 days — demonstrating remarkable longevity. Separately, the pH-responsive drug release capability was also confirmed under acidic conditions. The platform effectively neutralized multiple ROS species in vitro and significantly restored endothelial barrier integrity by inhibiting the ROCK/MLC pathway. In a laser-induced choroidal neovascularization model, a single injection suppressed pathological angiogenesis by 45%. In diabetic mice, the same treatment markedly reduced vascular leakage, attenuated neuroinflammation, and restored retinal function, with b-wave amplitudes recovering to near-normal levels.Conclusion This study establishes a multi-faceted nanotherapeutic strategy that synergizes sustained, long-acting ROCK inhibition with innate antioxidant activity. Designed to be activated by the pathological cues of DR, including acidic pH and ROS, our approach precisely targets multiple pathological pathways, offering a promising and translatable paradigm for overcoming the limitations of current monotherapies.
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NEUROCHEMISTRY INTERNATIONAL
·
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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