Advanced Science
·
2026
·
IF 14.1
Weiyu Zhang,Zhongwei Yang,Yunfan Zhang,Longwei Wang,Xiaoyu Zhang,Jiahui Mao,Yizhi Dai,Yifan Yuan,Mingge Wang,Xin Yang,Xin Yu,Jing Liu,Chunying Chen
Periodontitis, a chronic inflammatory disease initiated and sustained by plaque microorganisms and host immune response, remains an intractable oral disease and a leading cause of tooth loss worldwide. Traditional mechanical debridement and adjunctive antibiotic or antiseptic therapy often shows limited efficacy due to the complex anatomical structure, concerns regarding antimicrobial resistance, and poor penetration and retention within the subgingival infection niche. To overcome this limitation, we designed a Mo-N coordinated nanozyme exhibiting synergistic mimetic activities of multiple enzymes, including peroxidase (POD)-like, oxidase (OXD)-like, and catalase (CAT)-like activity. Benefiting from Mo-N coordination and multi-enzyme mimetic behavior, Mo 5 N 6 nanozymes dynamically modulate local oxidative reactions within the gingival sulcus, thereby effectively damaging pathogenic bacteria while avoiding excessive oxidative stress. The nanozymes efficiently suppress anaerobic Gram-negative periodontal pathogens sensitive to elevated reactive oxygen species (ROS), facilitating efficient attenuation of pathogenic stimuli. This strategy not only enhances the periodontal microenvironment but also facilitates the restoration of commensal microbiota and regeneration of periodontal tissues, highlighting the therapeutic potential of Mo 5 N 6 nanozymes in periodontitis treatment.
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Advanced Healthcare Materials
·
2026
·
IF 11
Xiang Luo,Jiajun Xie,Fengxu Yan,Zhidong Peng,Chongzhi Pan,Yiming Hu,Jian Zhang,Changxiong Cai,Jinghong Yuan,Yang Li,Xinxin Miao,Dingwen He,Xigao Cheng
Localized oxidative stress and chronic inflammation driven by excessive accumulation of reactive oxygen species (ROS) represent central pathogenic forces that initiate and perpetuate the degenerative cascade underlying intervertebral disc degeneration (IVDD). Here, it is developed a pathological microenvironment–responsive catalytic carbon nanodot delivery platform (PPOD@CeCDs) featuring dual reversible covalent cross-linking mediated by phenylboronate ester and Schiff base bonds, which selectively senses the acidic and highly oxidative milieu characteristic of IVDD to enable on-demand release of cerium-doped carbon nanodots (CeCDs), thereby intercepting the ROS-driven inflammatory cascade at its oxidative origin. PPOD@CeCDs exhibits favorable injectability, controllable degradability, biocompatibility, and robust antioxidant activity, together with stable intradiscal retention and stimulus-responsive release under pathological conditions. In vitro, PPOD@CeCDs protects nucleus pulposus (NP) cells from oxidative injury, suppresses inflammation amplification by modulating the ROS-driven PI3K–Akt–NF-κB signaling axis, regulates macrophage polarization, and preserves extracellular matrix homeostasis. In a rat model of IVDD, intradiscal injection of PPOD@CeCDs mitigates matrix degradation and promotes structural restoration of degenerative discs. Collectively, by integrating a microenvironment-responsive hydrogel with catalytically active carbon nanodots, this strategy sustainably intercepts ROS-driven inflammatory cascades and offers a mechanistically defined, translationally promising therapeutic approach for IVDD.
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ACS Applied Materials & Interfaces
·
2026
·
IF 7.8
Peili Li,Siyu Zhang,Haoran Xu,Xiangxiang Wu,Xiaoqing Yu,Wenxin Wang,Ran Ding,Da Zhang,Junhua Chen,Xiang Ke,Zirong Li
Bacterial infections associated with biofilm formation hinder wound healing via enhanced antibiotic resistance and impaired tissue repair. Herein, we fabricated dandelion herb-derived carbon dots (DH-CDs) through a green solvothermal-extraction method, developing a biocompatible antimicrobial agent with synergistic wound healing potential. Physicochemical characterization showed that DH-CDs are quasi-spherical (4.87 nm), partially graphitized nanoparticles with abundant surface functional groups and pH-responsive charge-switching capability. In vitro studies demonstrated that DH-CDs exhibit broad-spectrum antibacterial activity against S. aureus and E. coli, with minimum inhibitory concentrations (MICs) of 62.5 μg/mL at pH 7.4 and 31.25 μg/mL at pH 5.5. The antibacterial effect is mediated by a multimodal mechanism involving electrostatically driven bacterial membrane disruption, energy metabolism inhibition, intracellular reactive oxygen species (ROS) generation, and antioxidant enzyme inactivation. Moreover, DH-CDs achieve complete disruption of mature S. aureus biofilms at 300 μg/mL. Notably, DH-CDs possess excellent biocompatibility, with a 10% hemolysis concentration (HC10) exceeding 4000 μg/mL and over 95% viability of NIH 3T3 fibroblasts at 2000 μg/mL. A unique dual ROS-modulating capability was identified that DH-CDs generate excessive ROS to eradicate bacteria while scavenging deleterious ROS in mammalian cells, thereby preserving redox homeostasis. In vivo evaluations in a murine S. aureus-infected full-thickness wound model demonstrated that DH-CDs significantly accelerate wound closure by promoting re-epithelialization, granulation tissue maturation, collagen deposition, and hair follicle regeneration, outperforming a commercial wound healing spray. Collectively, DH-CDs integrate green synthesis, pH-responsive antibacterial/antibiofilm activity, dual ROS regulation, and biocompatibility, representing a promising translational candidate for bacteria-infected wounds and a paradigm for multifunctional biomass-derived nanomaterials.
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MATERIALS & DESIGN
·
2023
·
IF 8.4
Haiting Xu,Linxin Dai,Wenbiao Nie,Ruifeng Luo,Xiulan Pu,Lingling Dong,Qiyan Chen,Shanshan Qi,Xiaoqin Han,Jieshu You,Jinming Zhang,Fei Gao
Cyclodextrins (CDs) have been applied widely as an oral micro-nano drug delivery material for the treatment of ulcerative colitis (UC) because of their stability around the stomach. However, the further application of CDs is hindered due to their inherent poor targeting and controlled release properties. In this study, CD-supramolecular nanoparticles ( [email protected] ) were developed based on the structural characteristics of CDs (e.g., multi-group modifiability and hydrophobic cavity) to encapsulate rhein (RH) for oral delivery against UC. The [email protected] showed an average size of 154.70 ± 1.80 nm and exhibited high encapsulation efficiency (95.55 ± 2.37 %). When incubated in simulated gastric fluid for 2 h, [email protected] only released 20.3 ± 0.47 % RH due to the protection of supramolecular effects of CDs. However, RH was rapidly released from [email protected] (released 66.3 ± 2.50 %) after H 2 O 2 was treated with the assistance of the ROS-sensitive properties. Moreover, [email protected] were taken up by macrophages in 1.5 times higher amounts than preparations which did not have CD44-targeted effects. Notably, the results showed that [email protected] with an accurate on-demand drug release strategy achieved the best anti-inflammatory and antioxidant effects, and they are expected to be a promising carrier in the UC treatment.
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Biomaterials Advances
·
2022
·
IF 0
Xin Mu,Yulei Chang,Ying Bao,Anni Cui,Xiahua Zhong,Griffin B. Cooper,Anika Guo,Guiye Shan
Photodynamic therapy (PDT) efficiency is directly affected by the reactive oxygen species (ROS) generated by photosensitizers. However, ROSs' ultrashort life span and limited diffusion distance restrict the PDT efficiency. Therefore, it is important to control the delivery strategy of photosensitizers for PDT treatment. Herein, the core-satellite nanoreactors were fabricated with oxygen generation and ROS diffusion properties. The hollow CuS encapsulating horseradish peroxidase (HRP) was combined with the cationic photosensitizers (PEI-Ce6). The unique photosensitizers delivery strategy makes the nanoreactors achieve ROS diffusion-enhanced PDT effect. First, HRP in “core” (HRP@CuS) can decompose hydrogen peroxide (H 2 O 2 ) to O 2 , increasing O 2 levels on the surface of the nanoreactor. Second, the Ce6 molecules covalent-linked with PEI are uniformly dispersed on the surface of CuS as a “satellite”, avoiding Ce6 aggregation and causing more Ce6 molecules be activated to produce more 1 O 2 . Due to the Ce6 was on the surface of the CuS nanocages, the generated ROS may ensure a larger diffusion range. Meanwhile, the inherently CuS nanocages exhibit photothermal and photoacoustic (PA) effect. The photothermal effect further enhances the ROS diffusion. Under the guidance of PA imaging, nanoreactors exhibit highly efficient hypoxic tumor ablation via photodynamic and photothermal effect. Overall, the core-satellite nanoreactors provide an effective strategy for tumor therapy, further promoting the research of photosensitizers delivery.
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MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Boyang Cheng,Xindang Chu,Ruiwen Liu,Xinyuan Ma,Mengyang Wang,Jiayi Zhang,Pingxuan Jiao,Qianqian Gao,Wenxiao Ma,Yongmin Zhang,Chuanke Zhao,Demin Zhou,Sulong Xiao
Betulinic acid (BA) and oleanolic acid (OA) are plant-derived conjugates found in various medicinal plants that have emerged as potential antitumor agents. Herein, a series of novel BA and OA derivatives were synthesized by conjugation with per-O-methylated-β-cyclodextrin (PM-β-CD), and their anticancer properties against a panel of three human cancer cell lines were evaluated. Two OA-PM-β-CD conjugates (48 and 50) were observed to be the most potent conjugates against the three cell lines (MCF-7, BGC-823, and HL-60), with a 15- to 20-fold decrease in the IC50 values (IC50: 6.06–8.47 μM) compared with their parental conjugate (OA). Annexin V-FITC/propidium iodide staining and Western blot analysis revealed that both conjugates induced apoptosis in HL-60 cells. Additionally, in the representative conjugate 48-treated HL-60 cells, a decrease in mitochondrial membrane potential and subsequent release of cytochrome c into the cytosol were observed, indicating the activation of the intrinsic apoptosis pathway. Furthermore, 48 dramatically induced the generation of reactive oxygen species (ROS) in HL-60 cells, and the corresponding effect could be reversed using the ROS scavenger N-acetylcysteine. Collectively, these results suggest that the novel pentacyclic triterpenoid derivatives trigger the intrinsic apoptotic pathways via the ROS-mediated activation of caspase-3 signaling, inducing cell death in human cancer cells.
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Acta Biomaterialia
·
2023
·
IF 9.7
Xiaoli Feng,Tian Lin,Dong Chen,Zhiyang Li,Qiuping Yang,Huiting Tian,Yao Xiao,Mingzhen Lin,Min Liang,Weihong Guo,Peng Zhao,Zhaoze Guo
Chemodynamic therapy (CDT) can effectively induce immunogenic cell death (ICD) in tumours and is thus a promising strategy for boosting the efficacy of immunotherapy. However, the mechanism by which CDT enhances ICD and lowers ICD efficiency is unknown and this restricts its clinical application. In this study, a second near-infrared (NIR-II) window irradiation-triggered hydrogen peroxide (H 2 O 2 ) self-supplying nanocomposite ((Cu 2 Se-CaO 2 )@LA) was constructed. The modified lauric acid was melted by the heat energy of the NIR-II irradiation, to expose the CaO 2 nanoparticles, and they then reacted with water to produce H 2 O 2 and Ca 2+ . H 2 O 2 was then converted to hydroxyl radicals by the photothermal-enhanced CDT process of the Cu 2 Se nanocubes. Notably, the CDT and Ca 2+ overload was found to induce sequential damage to the mitochondria and endoplasmic reticulum (ER), which upregulated the PERK-mediated eIF2α phosphorylation pathway and caused subsequent ICD. NIR-II irradiation of the (Cu 2 Se-CaO 2 )@LA also increased reactive oxygen species (ROS) formation and this was sufficient to increase dendritic cell maturation, attracting cytotoxic T lymphocytes, and suppressing tumour growth in vivo. Overall, we demonstrated that an enhanced CDT strategy under NIR-II exposure and H 2 O 2 self-supply can induce extensive ICD by inducing mitochondria-associated ER stress, which represents a highly effective and promising strategy for ICD amplification and tumour immunotherapy. Statement of significance In this study, a second near-infrared window (NIR-II) irradiation-triggered and H 2 O 2 self-supplying nanocomposite (named (Cu 2 Se-CaO 2 )@LA) was constructed and tested both in vitro and in vivo . These nanoparticles demonstrated promising antitumor activity as designed. Mechanistically, the nanoparticles could damage mitochondria and upregulate the PERK-mediated eIF2αphosphorylation pathway, further causing endoplasmic reticulum stress, and inducing immunogenic cell death through dendritic cell maturation and cytotoxic T lymphocyte recruitment augmented activity. This system represents a highly effective and promising strategy for enhancing tumor immunotherapy and provides new insights for future studies and design refinements.
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FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Xinyue Sun,Wenyue Zhang,Yuqi Wang,Yilei Zhang,Xiaojing Liu,Xu Shi,Shiwen Xu
Di(2-ethylhexyl) phthalate (DEHP) and polystyrene microplastics (PS-MPs) are new environmental pollutants that attracted increased attention. At present, the effects and underlying mechanisms of action of combined exposure of DEHP and PS-MPs on the kidney have not been elucidated. To investigate the renal toxicity of DEHP and PS-MPs exposure, we established single and combined DEHP and PS-MPs exposure models in mice and HEK293 cells, respectively. Hematoxylin and eosin staining, transmission electron microscopy , monodansylcadaverine staining, immunofluorescence, real-time quantitative PCR, Western blot analysis and other methods were used to detect relevant indicators. The results showed that the expression levels of ROS/AMPK/ULK1 and Ppargc1α/Mfn2 signaling pathway-related genes were significantly increased in the DEHP and PS-MPs exposure models. The mRNA and protein expression levels of autophagy markers were also upregulated. In addition, we found that the expression levels of mRNAs and proteins in the combined exposure group were more significantly increased than those in the single exposure group. In conclusion, combined exposure to DEHP and PS-MPs caused oxidative stress and activated the AMPK/ULK1 pathway, thereby inducing renal autophagy. Our results enhance the field of nephrotoxicity studies of plasticizers and microplastics and provide new light on combined toxicity studies of DEHP and PS-MPs.
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BIOMATERIALS
·
2022
·
IF 15.304
Hongjie Zhang,Weijian Chen,Jing Wang,Wenxiang Du,Bibo Wang,Lei Song,Yuan Hu,Xiaopeng Ma
Reactive oxygen species (ROS) as well-known endogenous stimuli has been widely used to activate drug delivery systems (DDSs) for tumor-specific therapy. Unfortunately, endogenous ROS in the tumor microenvironment (TME) is not enough to achieve effective therapeutic efficacy and cancer cells have adapted to high oxidative stress by upregulating glutathione (GSH) level. Herein, we devised a novel ROS-activable self-immolative prodrug CASDB with both GSH-depletion ability and ROS self-supply competence. Then, an stimuli-responsive nanoplatform integrating CASDB with clinical chemotherapeutics mitoxantrone (MTO) and PLGA was fabricated (denoted as CMPs) through nanoprecipitation method. The CMPs could achieve desired accumulation at tumor tissues through enhanced permeability and retention (EPR) effects. Then the accumulated CMPs could induce tumor cell apoptosis efficiently. Especially, ROS in tumor sites could trigger the immolation of CASDB to generate CA and quinone methide (QM). Then CA and QM cooperatively promoted damage of mitochondria due to oxidative stress and led to cancer cells more sensitive to MTO. Accordingly, MTO could perturb cellular microenvironment of cancer cells then promote the degradation of CASDB. The experiment results demonstrated that CMPs were ideal for desirable synergetic tumor-specific anticancer therapy with negligible systemic toxicity. The half-maximal inhibitory concentrations (IC50) value of CMPs was 6.53 μM, while the IC50 values of MTO was 14.76 μM. And the CMPs group showed the strongest tumor suppressor effect with the tumor sizes increased to 1.2-fold (Control group: 20.6-fold, MTO only: 3.0-fold). This study should be inspirational for designing efficient prodrugs to overcome the handicaps of traditional chemotherapy.
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Advanced Healthcare Materials
·
2023
·Vol. 12
·期 10
·2203195
·
IF 10
Zhongyin Zhang,Lichan Yuan,Yufeng Liu,Ruobing Wang,Yihong Zhang,Yan Yang,Hui Wei,Junqing Ma
Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative joint disease with no complete cure at present. Notably, the inflammatory microenvironment in TMJ OA is modulated by oxidative stress, which impacts cartilage metabolism, chondrocyte apoptosis, inflammatory cytokine release, and extracellular matrix (ECM) synthesis. Thus, it is reasoned that reducing excess reactive oxygen species (ROS) in the chondrocyte microenvironment may be an effective therapeutic strategy for TMJ OA. Recently, cascade nanozymes, including Pt@PCN222-Mn, have been exploited to treat ROS-associated diseases. Nevertheless, cascade nanozymes are not employed for TMJ OA therapy. To fill this gap, it is explored whether the Pt@PCN222-Mn cascade nanozyme could be applied to the treatment of TMJ OA. The in vitro results demonstrate that the Pt@PCN222-Mn nanozyme can inhibit the production of inflammatory factors, the degradation of ECM, and the apoptosis of chondrocytes by inhibiting the ROS-nuclear factor kappa-B (NF- κ B_ and mitogen-activated protein kinase signaling pathways. The in vivo results further demonstrate that the Pt@PCN222-Mn nanozyme can delay the progression of TMJ OA in the rat unilateral anterior crossbite model. It is believed that insightful perspectives on the application of nanozymes in TMJ OA will be provided here.
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PHARMACOLOGICAL RESEARCH
·
2022
·
IF 10.334
Liyun Zheng,Shiji Fang,Aifang Chen,Weiqian Chen,Enqi Qiao,Minjiang Chen,Gaofeng Shu,Dengke Zhang,Chunli Kong,Qiaoyou Weng,Suqin Xu,Zhongwei Zhao,Jiansong Ji
Sorafenib , a multikinase inhibitor, is the first-line agent for advanced liver cancer. Sorafenib strongly inhibits both cell proliferation and tumour angiogenesis. However, the development of drug resistance hampers its anticancer efficacy. To improve the antitumour activity of sorafenib, we demonstrate that piperlongumine (PL), an alkaloid isolated from the fruits and roots of Piper longum L ., enhances the cytotoxicity of sorafenib in HCCLM3 and SMMC7721 cells using the cell counting kit-8 test. Flow cytometry analysis indicated that PL and sorafenib cotreatment induced robust reactive oxygen species (ROS) generation and mitochondrial dysfunction, thereby increasing the number of apoptotic cells and the ratio of G2/M phase cells in both HCCLM3 and SMMC7721 cells. Furthermore, AMP-protein kinase (AMPK) signalling was activated by excess ROS accumulation and mediated growth inhibition in response to PL and sorafenib cotreatment. RNA-sequencing analysis indicated that PL treatment disrupted RNA processing in HCCLM3 cells. In particular, PL treatment decreased the expression of cleavage and polyadenylation specificity factor 7 (CPSF7), a subunit of cleavage factor I , in a time- and concentration-dependent manner in HCCLM3 and SMMC7721 cells. CPSF7 knockdown using a gene interference strategy promoted growth inhibition of PL or sorafenib monotherapy , whereas CPSF7 overexpression alleviated the cytotoxicity of sorafenib in cultured liver cancer cells. Finally, PL and sorafenib coadministration significantly reduced the weight and volume of HCCLM3 cell xenografts in vivo. Taken together, our data indicate that PL displays potential synergistic antitumour activity in combination with sorafenib in liver cancer.
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Nanoscale
·
2022
·Vol. 14
·期 13
·5054-5067
·
IF 8.307
Beibei Zhang,Rui Xue,Chunyang Sun
Glioblastoma (GBM) is the most lethal primary intracranial tumor because of its high invasiveness and recurrence. Therefore, nanocarriers with blood–brain barrier (BBB) penetration and transcranial-controlled drug release and activation are rather attractive options for glioblastoma treatment. Herein, we designed a multifunctional nanocarrier (T-TKNPVP) that combined targeted X-ray-induced photodynamic therapy (X-PDT) and cascaded reactive oxygen species (ROS)-boosted chemotherapy. The T-TKNPVP loaded with verteporfin (VP) and paclitaxel (PTX) was self-assembled from an angiopep-2 (Ang) peptide, functionalized Ang-PEG-DSPE and ROS-sensitive PEG-TK-PTX conjugate. After systemic injection, the T-TKNPVP efficiently crossed the BBB and targeted the GBM cells via receptor-mediated transcytosis. Upon X-ray irradiation, they can generate a certain amount of ROS, which not only induces X-PDT but also locoregionally activates PTX release and action by cleaving the TK bridged bonds. As evidenced by 9.4 T MRI and other experiments, such nanocarriers offer significant growth inhibition of GBM in situ and prolong the survival times of U87-MG tumor-bearing mice. Taken together, the designed T-TKNPVP provided an alternative avenue for realizing transcranial X-PDT and X-ray-activated chemotherapy for targeted and locoregional GBM treatment in vivo.
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