COMPOSITES PART B-ENGINEERING
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2025
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IF 14.2
Yiran Zhang,Qingcheng Song,Shuai Yang,Jiheng Xiao,Fengkun Wang,Chunxu Fu,Xin Xing,Jianhua Wu,Shuo Zhang,Yanbin Zhu,Yingze Zhang
Osteoporotic bone defects (OBDs) pose significant clinical challenges due to impaired tissue regeneration and osteogenic differentiation. Conventional combination therapies using systemic anti-osteoporosis drugs and graft fillings have yielded unsatisfactory results. Excessive reactive oxygen species (ROS) are a hallmark of OBDs, leading to abnormal inflammatory responses and a hostile osteoimmune microenvironment that impedes repair. In this study, we developed a multifunctional injectable hydrogel, termed PTSr@CP, composed of a strontium (Sr) and tannic acid (TA)-based metal–phenolic network core coated with polydopamine (PDA), integrated into a matrix of carboxymethyl chitosan and poly (γ-glutamic acid). The PTSr@CP hydrogel can be easily injected into bone defect sites, where it undergoes rapid in situ crosslinking and exhibits exceptional ROS-scavenging capabilities. Additionally, the hydrogel mediates mild photothermal therapy (MPTT), promoting local tissue repair. Both in vitro and in vivo studies demonstrated its excellent biosafety and confirmed synergistic bone regeneration through enhanced osteogenesis, angiogenesis, and osteoimmunomodulation. This work offers a compelling strategy for OBD treatment by combining mild hyperthermia-enhanced in situ bone repair with sustained delivery of bioactive agents to improve the osteoimmune microenvironment.
研究领域:
生物材料学
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骨科医学
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再生医学
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EMBO REPORTS
·
2024
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IF 6.5
RenXiaoyu,ShiPeng,SuJing,WeiTonghua,LiJiayi,HuYiping,WuCongying
Tumor metastasis involves cells migrating directionally in response to external chemical signals. Reactive oxygen species (ROS) in the form of H2O2 has been demonstrated as a chemoattractant for neutrophils but its spatial characteristics in tumor microenvironment and potential role in tumor cell dissemination remain unknown. Here we investigate the spatial ROS distribution in 3D tumor spheroids and identify a ROS concentration gradient in spheroid periphery, which projects into a H2O2 gradient in tumor microenvironment. We further reveal the role of H2O2 gradient to induce chemotaxis of tumor cells by activating Src and subsequently inhibiting RhoA. Finally, we observe that the absence of mitochondria cristae remodeling proteins including the mitochondria-localized actin motor Myosin 19 (Myo19) enhances ROS gradient and promotes tumor dissemination. Myo19 downregulation is seen in many tumors, and Myo19 expression is negatively associated with tumor metastasis in vivo. Together, our study reveals the chemoattractant role of tumor microenvironmental ROS and implies the potential impact of mitochondria cristae disorganization on tumor invasion and metastasis.
研究领域:
肿瘤生物学
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细胞生物学
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医学
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PubMed
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Advanced Healthcare Materials
·
2026
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IF 11
Yan Zhang,Song Li,Qiang Li,Ruiyuan Wang,Yue Sun,Yichun Wang,Xiaomin Yan,Xiaojian Wang,Yufeng Wang,Yadong Xue,Chao Ding,Jianfeng Gong,Lin Ding,Huangxian Ju
Conventional targeted therapies for inflammatory bowel disease (IBD) often rely on unstable biological recognition elements. While molecularly imprinted polymers (MIP) offer robust synthetic alternatives, their utility is limited by an “always-on” binding state: even weak non-specific adsorption can significantly compromise their target-binding capacity. We convert static MIP into reactive oxygen species (ROS)-activated therapeutic actuators by conjugating mannose to transferrin-imprinted MIP via a ROS-cleavable linker. The saccharide acts dually as a therapeutic agent and a protective cloak. It sterically blocks non-specific binding during intestinal transit. At inflammatory sites, elevated ROS levels (higher than in healthy tissue) trigger simultaneous mannose release and activation of high-affinity targeting. This enables precise MIP anchoring to the inflamed epithelium for physical barrier formation and localized microbiome modulation. In murine colitis models, this achieved mucosal healing, mitigated inflammation, and microbiota rebalancing using a mannose equivalent dose of 27.2 mg/kg/d, benchmarking against free mannose and non-responsive MIP controls. This work establishes a generalizable paradigm for targeted recognition and drug delivery in complex physiological environments, paving the way for intelligent, disease-responsive nanomedicines.
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Nano Today
·
2023
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IF 17.4
Zhijiang Guo,Qiong Chen,Taibo Liang,Baoyuan Zhou,Suhua Huang,Xiufeng Cao,Xiuli Wang,Zaisong Ding,Jiangping Tu
The reactive oxygen species (ROS) wave plays a crucial role as an early systemic signal in nearly all environmental response pathways. Engineering on ROS signaling may be a promising strategy to modulate plant systemic acquired acclimation and systemic acquired resistance . Recently, artificial designed materials mimicking signal transduction components have attracted attention to improve plant immunity and stress acclimation. Here, we report the bioengineering of functional carbon nanoparticles (FCN) through their regulation on ROS signaling. FCN with a C:O atom ratio of 1:2.2 were synthesized by low voltage electrolysis with graphite and carboxyl were the main oxygen-containing groups on the surface of sp 2 carbon core. The active redox properties resulting from the carboxyl–rich modification provided FCN superior ROS-triggering effects compared to other carbon nanoparticles with similar core structures but different types and quantities of surface modifications. Moreover, the ROS induced by FCN were quickly scavenged to homeostasis without causing accumulation and then leading to oxidative stress . The findings from transcriptional footprinting in Arabidopsis ’s genes revealed a typical and quick ROS signal transduction events and also the regulation of stress responses and adaptions to biotic and abiotic stresses . In addition, the application of FCN to roots have been shown to promote the growth and development of Arabidopsis , rice and wheat, and also the yields particularly when suffering stresses. In summary, our findings confirmed that the ROS burst triggered by FCN modulated the balance between growth and defense through transcriptome reprogramming. It indicates that nano-enabled plant engineering for ROS can provide an economical and efficient way to promote the crops yields, especially under stress conditions.
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ACS Applied Nano Materials
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2023
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IF 5.9
Weihua Su,Yan Qin,Jianning Wu,Guihua Meng,Shengchao Yang,Lin Cui,Zhiyong Liu,Xuhong Guo
After cotton is invaded by cotton aphids and other pests, the function of its defense system decreases, and it is more vulnerable to infection by bacteria. When plants are invaded by external bacteria, they quickly produce reactive oxygen species (ROS). In this paper, ROS-responsive pesticide release carrier materials are designed and prepared for solving bacterial infections in plants by ring-opening polymerization of ε-caprolactone (ε-CL) and β-cyclodextrin (β-CD) to obtain a hydrophobic guest (β-CD-PCL). Thioketal (TK) was modified by adamantane (Ad) and poly(ethylene glycol) monomethyl ether (mPEG5000-OH) to form a hydrophilic guest (mPEG5000-TK-Ad). β-CD-PCL and mPEG5000-TK-Ad interact with each other to form an amphiphilic polymer (mPEG5000-TK-Ad@β-CD-PCL), which is loaded with carbendazim (MBC) by self-assembly (MBC-mPEG5000-TK-Ad@β-CD-PCL). The polymer had ROS response characteristics, and the release rate of C increased from 30 to 57% after 120 h of ROS stimulation. The inhibition rate of Rhizoctonia S. was 92.23% when the effective concentration of MBC was 30 mg/L. The critical micelle concentration (CMC) of the polymer is 8.30 mg/L, and the micelle had storage stability for at least 14 days, showing good storage stability. Therefore, this ROS-responsive polymer carrier has great potential as a carrier for antimicrobial pesticides.
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高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 14
·4930-4937
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IF 6.6
Birong Fan,Wan Peng,Yu Zhang,Pingsheng Liu,Jian Shen
Photodynamic therapy (PDT) is becoming an efficient antibacterial strategy without drug-resistance. Here, we report a promising reactive oxygen species (ROS) conversion strategy to increase the antibacterial efficiency of an Eosin Y (EOS)-based PDT system. Based on visible-light illumination, EOS generates a high concentration of singlet oxygen (1O2) in the solution. With the introduction of HEPES in the EOS system, it can almost completely convert 1O2 to hydrogen peroxide (H2O2). The orders-of-magnitude increases in the half-lives of the ROS (H2O2vs.1O2) present in the solution can enable more persistent oxidation ability. Thus, it is able to increase the bactericidal efficiency (against S. aureus) from 37.9% to 99.9%, promote the inactivation efficiency of methicillin-resistant S. aureus (MRSA) from 26.9% to 99.4%, and enhance the eradication rate of MRSA biofilm from 69% to 90%. Further in vivo investigation showed that the increased oxidation ability of the EOS/HEPES PDT system can enable quicker healing and maturing (even better than that for vancomycin administration) of MRSA-infected skin wounds on rats. This strategy may find many creative applications for the efficient eradication of bacteria and other pathogenic microorganisms.
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Zishan Zeng,Yong Luo,Xiaoyu Xu,Ting Shan,Meixu Chen,Zeqian Huang,Yanjuan Huang,Chunshun Zhao
Mitochondrion is an ideal target for amplifying ROS attack in antitumor treatment. Benefiting from distinctive properties of mitochondria, the precise delivery of ROS generator to mitochondria could maximumly utilize ROS for oxidation therapy. Herein, we prepared an innovative ROS-activatable nanoprodrug (HTCF) which dually targets tumor cells and mitochondria for antitumor therapy. Cinnamaldehyde (CA) was conjugated to ferrocene (Fc) and triphenylphosphine by thioacetal linker, to synthesize mitochondria-targeting ROS-activated prodrug (TPP-CA-Fc), which subsequently self-assembled into nanoprodrug via host-guest interactions between TPP-CA-Fc and cyclodextrin-decorated hyaluronic acid conjugate. Under mitochondrial high ROS condition, especially in tumor cells, HTCF selectively initiate in-situ Fenton reaction to catalyze H 2 O 2 into highly cytotoxic •OH, ensuring maximum generation and utilization of •OH for precision CDT. Meanwhile, the mitochondrial high ROS trigger thioacetal bond cleavage and CA release. The released CA stimulate mitochondrial oxidative stress aggravation and H 2 O 2 regeneration, which in turn react with Fc for more •OH generation, forming self-amplifying positive feedback cycle of CA release and ROS burst. With self-augmented Fenton reaction and mitochondria-specific destruction, HTCF ultimately induce intracellular ROS burst and severe mitochondrial dysfunction for amplified ROS-mediated antitumor therapy. Such an ingenious organelles-specialized nanomedicine exhibited prominent antitumor effect both in vitro and in vivo, revealing underlying perspectives to amplify tumor-specific oxidation therapy.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
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IF 5.8
Qiqi Sun,Jun Chen,Quan Zhao,Ziyun He,Lei Tang,Yuji Pu,Bin He
Ulcerative colitis (UC) as an important type of inflammatory bowel disease is a chronic disease characterized by intestinal dyshomeostasis. The UC treatment is challenged by the insufficiency of drug delivery and retention. Herein, we fabricated an intrarectal formulation of olsalazine (Olsa)-loaded hydrogel microspheres (LDKT/Olsa) with good bio-adhesiveness and reactive oxygen species (ROS)-scavenging ability to enhance drug retention and therapeutic effect. Low methoxy pectin-dopamine conjugate/konjac glucomannan composite hydrogel microspheres (LDKT) with a size ranging from 10 to 100 μm were prepared by using Zn 2+ and ROS-sensitive thioketal as crosslinkers. Upon intrarectal administration, the negatively charged and dopamine-functionalized hydrogel microspheres efficiently adhered to cationic surface of inflammatory mucosa, scavenging ROS and releasing Zn 2+ and Olsa for antibacterial and anti-inflammatory effects. In the dextran sodium sulfate (DSS)-induced mouse UC model, the microspheres significantly reduced the levels of colonic ROS and pro-inflammatory cytokines, improved gut mucosal barrier integrity, and remarkably relieved colitis . Overall, the LDKT microspheres are promising carriers to deliver drugs for UC treatment.
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CHEMICAL ENGINEERING JOURNAL
·
2023
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IF 15.1
Yingwen Lu,Pengfei Shan,Weilin Lu,Xiangping Yin,Haiwei Liu,Xiaoyue Lian,Jiayi Jin,Yuxi Qi,Zhongyu Li,Zhihui Li
Bacterial infection is a serious global health threat, and the clinical abuse of antibiotics has severe systemic toxicity and leads to multidrug-resistant bacteria. Stimuli-responsive polymers represent an encouraging strategy for intelligent treatment; however, inadequate polymer degradation and drug release are still challenging, especially in bacterial infection, where exponential rates of degradation and release are urgently needed. Here, we reported a facile 1,1,3,3-tetramethylguanidine (TMG)-promoted polyesterification method for the preparation of a novel antibiotic-free, PEGylated ROS-responsive polymeric prodrug of cinnamaldehyde (PRPCA), and demonstrated its remarkable intrinsic antibacterial activities and the acceleration of infected wound healing for the first time. The CA was covalently incorporated into the backbone of the polyester by a ROS-responsive thioacetal linkage and can be triggered to release by the ROS generated during bacterial growth. The released CA successively induced more ROS generation and the polymer achieved self-accelerating degradation via the positive feedback. The PRPCA-based nanomedicine possessed great bactericidal effects against both S. aureus and E. coli in vitro . Strikingly, the self-amplifying degradation of PRPCA nanoparticles caused abrupt “self-destruction” of S. aureus . More importantly, PRPCA significantly accelerated the S. aureus -infected wound healing process without systematic toxicity. Collectively, this work opens an avenue to develop novel self-amplifying stimuli-responsive polymers based on natural antimicrobial for superior wound disinfection and healing.
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Materials Science & Engineering C-Materials for Biological Applications
·
2019
·
IF 4.959
Zhiyong Song,Yang Wu,Huajuan Wang,Heyou Han
Due to their remarkable antibacterial properties, silver nanoparticles (Ag NPs) and curcumin (CCM) have been widely used in the antimicrobial field. In our study, we have fabricated the uniform and stable silver/curcumin composite nanoparticles by a facile ultrasound treatment process and the synergistic antibacterial activity were evaluated. The curcumin not only played a role of reducing agent but also acted as a capping agent. The antibacterial effects of silver/curcumin (cAgNPs) were studied by measuring the growth curve and surface plate assay based on the E. coli and B. subtilis , which showed concentration dependent bacteriostatic and bactericidal effects of cAgNPs. The presence of CCM enhance the binding of Ag to bacterial membrane and Ag + release in comparison to that without CCM, so that creating a temporary and local high Ag + concentration near the surface of the bacterium, meanwhile, generation of more reactive oxygen species, lead to membrane damage, bacterial lipases and induce leakage of intracellular contents followed by bacterial death that lead to growth inhibition of the bacteria. The antibacterial effects were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), the effect which were further found to decrease by introducing antioxidant N -acetyl- l -cysteine (NAC) act as a reactive oxygen species (ROS) scavenging agent. These initial data suggest that cAgNPs have a highly antibacterial efficient and might have potential to be developed as an effective antimicrobial nanomaterial.
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JOURNAL OF INORGANIC BIOCHEMISTRY
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2019
·
IF 3.224
Jin-can Chen,Yao Zhang,Xin-ming Jie,Ji She,Guang-zhi Dongye,Yu Zhong,Yuan-yuan Deng,Jie Wang,Bo-yang Guo,Lan-mei Chen
Thioredoxin reductase (TrxR), a major component of the thioredoxin system, makes a critical role in regulating cellular redox signaling and is found to be overexpressed in many human cancer cells. TrxR has become an attractive target for anticancer agents . In this work, three Ru(II) complexes with salicylate as ligand, [Ru(phen) 2 (SA)] (phen = 1,10-phenanthroline, SA = salicylate, 1 ), [Ru(dmb) 2 (SA)] (dmb = 4,4′-dimethyl-2,2′-bipyridine, 2 ) and [Ru(bpy) 2 (SA)] (bpy = 2,2′-bipyridine, 3 ), were synthesized and characterized. The anticancer effect exerted by them was evaluated. Complex 1 was found to exhibit obvious anticancer activity , in comparison with cisplatin , against cancer cell lines, while displaying low toxicity to the normal cell line BEAS-2B. The mechanism of complex 1 cancer cell growth suppress was investigated in A549 cells. Complex 1 exerted its anticancer through inducing apoptosis and triggering cell cycle arrest at the G0/G1 phase. Complex 1 can selectively inhibit TrxR activity and thus promote the generation and accumulation of reactive oxygen species (ROS), which subsequently trigger mitochondrial dysfunction and DNA damage, activate oxidative stress-sensitive mitogen activated protein kinase (MAPK), and suppress the protein kinase B (PKB or AKT) signal pathway, resulting in apoptosis in A549 cells.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2019
·Vol. 17
·期 1
·1-12
·
IF 5.345
Zhao Bin,Zhao Penghe,Jin Zhaokui,Fan Mingjian,Meng Jin,He Qianjun
Background To improve the outcome of cancer treatment, the combination of multiple therapy models has proved to be effective and promising. Gas therapy (GT) and chemodynamic therapy (CDT), mainly targeting the mitochondrion and nucleus, respectively, are two emerging strategy for anti-cancer. The development of novel nanomedicine for integrating these new therapy models is greatly significant and highly desired. Methods A new nanomedicine is programmed by successive encapsulation of MnO 2 nanoparticles and iron carbonyl (FeCO) into mesoporous silica nanoparticle. By decoding the nanomedicine, acidity in the lysosome drives MnO 2 to generate ROS, ·OH among which further triggers the decomposition of FeCO into CO, realizing the effective combination of chemodynamic therapy with gas therapy for the first time. Results Acidity in the TEM drives MnO 2 to generate ROS, ∙OH among which further triggers the decomposition of FeCO into CO, realizing the effective combination of CDT and CDGT. The co-released ROS and CO do damage to DNA and mitochondria of various cancer cells, respectively. The mitochondrial damage can effectively cut off the ATP source required for DNA repair, causing a synergetic anti-cancer effect in vitro and in vivo. Conclusions The combination of CDT and CDGT causing a synergetic anti-cancer effect in vitro and in vivo. The proposed therapy concept and nanomedicine designing strategy might open a new window for engineering high-performance anti-cancer nanomedicine.
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