Applied Materials Today
·
2022
·
IF 8.663
Hao Xiong,Shuqin Wang,Zhenghua Sun,Juehong Li,Haolan Zhang,Weixuan Liu,Jihao Ruan,Shuai Chen,Changyou Gao,Cunyi Fan
Oxidative stress has close relationship with the progression of osteoarthritis and thus is an important therapeutic target. The use of antioxidants alone has common disadvantages such as low bioavailability, poor stability, and rapid joint clearance or toxicity at high concentrations. To achieve both reactive oxygen species (ROS) responsive scavenging ability and drug targeted delivery ability, a novel polymer (PEG-PTK-PEG) was synthesized through a simple and direct reaction between polythioketal (PTK) and m-PEG-acrylate. In addition to excellent mechanical properties and high drug loading capacity, the degradation products of PEG-PTK-PEG responding to the ROS accumulating microenvironment also have excellent biocompatibility and extremely low toxicity. Further, the PEG-PTK-PEG nanoparticles (NPs) loaded with astaxanthin (ASTA), which is an antioxidant with high biological safety, could effectively reduce ROS expression and release ASTA slowly and accurately in the area of high ROS expression as a result of the polymer degradation. In the OA model, the [email protected] could effectively inhibit the expression of ROS, thereby downregulating the MAPK signaling pathway and inducing the conversion of macrophages from the M1 phenotype to the M2 phenotype. The synergistic effect of PEG-PTK-PEG's ROS-responsive drug delivery ability and ROS scavenging ability significantly promoted the therapeutic effect of OA, providing a new and effective strategy for the clinical treatment of OA.
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CHEMICAL ENGINEERING JOURNAL
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2021
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IF 13.273
Yuxiang Sun,Li Xu,Xin Liu,Yaodong Shen,Yu Zhang,Ning Gu,Fei Xiong
Superoxide anion (O 2 •-), hydrogen peroxide (H 2 O 2 ), hydroxyl radical (•OH) are the main components of endogenous reactive oxygen species (ROS), while •OH shows the most significant cytotoxicity to tumor cells. Thus effective and continuous •OH generation is critical to ROS-based tumor treatment. Herein, we assembled coronal-shaped Fe 3 O 4 @CeO 2 nanoparticles (NPs) to achieve relay conversion of O 2 •- → H 2 O 2 → •OH in acute myeloid leukemia (AML) cells, where CeO 2 NPs function as the mimetic enzyme of superoxide dismutase (SOD) to convert O 2 •- → H 2 O 2 and Fe 3 O 4 NPs act as the peroxidase (POD) mimetic enzyme to realize H 2 O 2 → •OH. We found that assembled Fe 3 O 4 @CeO 2 got an enhanced POD activity and SOD activity due to the mechanism of more efficient relay conversion at sub-nanometer distance. As a result, assembled Fe 3 O 4 @CeO 2 successfully promoted the relay conversion of O 2 •- → H 2 O 2 → •OH in vitro and in AML cells, causing a continuous generation of •OH by utilizing the oxygen source of endogenous O 2 •- and endogenous H 2 O 2 . In AML cells, reportedly, O 2 •- and H 2 O 2 were both in high levels and the generation of O 2 •- is sustainable. Furthermore, Fe 3 O 4 @CeO 2 -driven the endogenous ROS axial conversion exacerbated AML cells apoptosis and prolonged the survival time of systemic AML mice, showing the worth of this relay conversion mechanism. Therefore, assembled Fe 3 O 4 @CeO 2 provides an ideal tool for the directed conversion of intracellular ROS and continuous generation of •OH. Importantly, the targeted conversion of ROS by assembling multi-enzyme system is an effective strategy for the intervention of ROS.
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Biomaterials Science
·
2017
·Vol. 5
·期 6
·1174-1182
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IF 4.21
Qiurong Deng,Xudong Li,Lipeng Zhu,Hua He,Donglai Chen,Yongbing Chen,Lichen Yin
The transfection performance of polycations is often hampered by various systemic barriers that pose conflicting requirements for material design. Herein, we developed fluorinated, ROS-cleavable polyethylenimine (PEI) for effective and serum-resistant gene delivery to cancer cells, by harmonizing the inconsistency between DNA condensation and release, and the inconsistency between cellular internalization and serum stability. Low-molecular weight (MW) PEI was cross-linked with a diselenide-containing linker and further modified with fluorocarbon chains. The obtained high-MW DSe-PEI-F has potent DNA condensation as well as intracellular DNA delivery capabilities, while in the cytoplasm of cancer cells, it can rapidly degrade into low-MW segments upon ROS treatment to promote DNA release and reduce the material toxicity. As such, DSe-PEI-F showed high transfection efficiencies in cancer cells in the presence of serum, outperforming the commercial reagent PEI 25k by several orders of magnitude. This study thus provides an effective approach to overcome various barriers against non-viral gene delivery, which contributes to the development of a new class of gene vectors with high efficiency and low toxicity.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-19
·
IF 12.6
Song Zhengwei,Sun Quanwei,Yang Wenshuo,Li Yunlong,Hu Chaoyu,Chen Chen,Liu Kang,Shen Wei,Yang Ye,Yin Dengke
Background Prolonging the duration of photodynamic therapy (PDT) enhances the level of reactive oxygen species (ROS), thereby facilitating tumor ablation. However, our findings indicated that excessive ROS not only induces epithelial-mesenchymal transition (EMT) but also creates an immunosuppressive microenvironment in tumor, thereby triggering tumor metastasis. Methods We initially developed neutrophil membrane hybrid liposomes (NLs) that can specifically target inflamed tumor tissues following PDT. Then, we utilized NLs to encapsulate the antioxidant nanozyme FeGA and the antiplatelet drug Lysine Acetylsalicylate (LAS), resulting in the formulation NLASF. Results Experimental results demonstrated that FeGA effectively scavenges ROS, thereby reversing the immunosuppressive microenvironment induced by prolonged PDT. Furthermore, the incorporation of LAS effectively disrupts the interaction between tumor cells and platelets, mitigating tumor EMT and inhibiting hematogenous tumor metastasis. In a breast cancer mouse model, we observed that treatment with NLASF led to a near-complete suppression of tumor lung metastasis following the prolonged PDT. Additionally, the in vivo application of NLASF did not result in any blood toxicity or organ toxicity, highlighting its significant advantages over the free drugs group. Conclusions This study provides a novel approach to enhance the efficacy of PDT and successfully suppress PDT-mediated tumor metastasis.
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CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yipeng Pang,Maofang Zhao,Yuhan Xie,Yanping Wang,Yuxin You,Yongding Ke,Chaoyi Zhang,Xiaohan Chen,Yijia Yang,Chunlei Zhang,Xi Chen,Yi Liu,Xingtang Fang
The development of non-antibiotic strategies for combating bacterial infections, particularly through reactive oxygen species (ROS) accumulation accompanying inflammation, has attracted much attention. Despite Allicin (Ac) emerges as a promising antimicrobial agent with wide and remarkable bioactivity, it still displays quite limited ROS scavenging and anti-inflammation capacity due to uncontrolled and poor bioavailability. Herein, a multifunctional nanoplatform with pH-dependent and ROS-scavenging antibacterial, anti-inflammatory and proangiogenic properties is introduced to promote infected wound healing by integrating Ac into silver nanoparticles (AgNPs)-loaded zeolite imidazole framework (ZIF-8), namely Ac@ZIF-8/AgNPs. Primarily, the nanoplatform is activated and controlled release in the infection microenvironment, with disrupting biofilms, scavenging ROS and antibacterial capacitys, outperforming conventional Ac. Moreover, in the mouse models induced by bacterial infection, Ac@ZIF-8/AgNPs can alleviate the inflammatory condition, scavenge ROS, facilitate the regeneration of collagen fiber and enhance vascular formation, collectively accelerating wound healing. Overall, this biocompatible nanoplatform is provided as a reliable approach to solve the long-standing problem of infected wound healing.
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Materials Today Bio
·
2025
·
IF 10.2
Ying Sun,Jiabao Xu,Ling Zou,Yan Tan,Jie Li,Haoran Xin,Yanli Guo,Weikai Kong,Dingyuan Tian,Xinyu Bao,Xiaoqin Wan,Xiaoxu Li,Zhihui Zhang,Xiaochao Yang,Fang Deng
Reperfusion through thrombolytic therapy or primary percutaneous coronary intervention is commonly used to deal with acute myocardial infarction. However, the reperfusion procedure is accompanied by myocardial ischemia-reperfusion injury (MIRI). Currently, there is no therapeutics that can effectively deal with MIRI in clinical practice. Herein, the potential of ceria nanoparticles (CNPs) coated by different ligands in the treatment of rat MIRI is evaluated. The results demonstrate that CNPs can effectively modulate the oxidative stress in the heart tissue through the elimination of reactive oxygen species (ROS) and stimulation of endogenous antioxidant system. The inhibition of oxidative stress results in the reduction of p-Drp1 (Ser 616) which is critical in driving the fission and fragmentation of mitochondria. The improved mitochondrial dynamics saves the cardiomyocytes from apoptosis and reduces the acute injury of left ventricular wall during the MIRI. The ejection function of the left ventricle for both the short-term and long-term MIRI rats is well preserved. We therefore believe based on these results that the administration of CNPs is beneficial in the attenuation of MIRI during the acute stage. These findings provide useful information for the future fabrication of inorganic antioxidant nanomedicine for the treatment of MIRI.
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Frontiers in Pharmacology
·
2025
·
IF 4.8
Meiying Li,Lili Wei,Wenxu Liu,Jiawen Wang,Qiujie Lu,Xianjue Chen,Lee Yong Lim,Jingxin Mo
Cerebral ischemia-reperfusion (I/R) injury is a major contributor to mortality and long-term disability worldwide, primarily due to excessive reactive oxygen species (ROS) generation after blood flow is restored. Although current treatments focus on reestablishing perfusion, they offer limited protection against the secondary ROS-mediated injury. Here, we report a multifunctional nanocomposite-graphene oxide loaded with glutathione (GSH) and functionalized with a fibrinogen-targeting aptamer (GO@GSH-FA)-capable of selectively releasing antioxidant cargo within the ischemic brain microenvironment. Characterization revealed a drug-loading capacity of 17.59% ± 3.74% and an entrapment efficiency of 78.78% ± 4.55%, highlighting the robust loading of GSH. The ROS-sensitive borate ester linker ensures that GSH is preferentially liberated in oxidative stress regions, while the fibrinogen aptamer actively targets fibrin-rich thrombotic sites. In vitro, GO@GSH-FA significantly restored viability in oxygen-glucose-deprived SH-SY5Y cells (from 31% up to near control levels), reduced inflammatory cytokines, and lowered intracellular ROS. In a Endothelin-1 (ET-1) induced cortical ischemia model, GO@GSH-FA led to a marked decrease in neurological deficit scores (from 7.20 ± 1.16 to 4.20 ± 0.98) and enhanced neuronal survival relative to untreated animals. Collectively, these findings underscore the promise of GO@GSH-FA as a targeted, ROS-responsive platform for mitigating cerebral I/R injury.
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ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Tingting Luan,Lulu Cheng,Ju Cheng,Xiaoyun Zhang,Yufei Cao,Xiangdong Zhang,Haiyan Cui,Guanghui Zhao
The reactive oxygen species (ROS)-responsive intelligent drug delivery system has developed rapidly in recent years. However, because of the low concentration of ROS in most types of tumor cells, it is not possible to rapidly and effectively stimulate the drug delivery system to release the active drug. Here, we introduced “sequential induced activation processes” for efficient tumor therapy by designing a new ROS-responsive drug release platform. β-Lapachone, a positively charged nitrogen mustard (NM) prodrug, and two diblock molecules (mPEG-AcMH and PAsp-AcMH) are self-assembled to form prodrug primary micelles, which are further aggregated into nanoparticles that facilitate drug codelivery. When administered by intravenous injection, the nanoparticles reach the tumor site and enter the tumor cells by endocytosis. The β-lapachone released in the tumor cells induces a large amount of H2O2, and the ROS-responsive NM prodrug is activated to form activated NM, quinone methide, and boric acid under the induction of H2O2. The activated NM leads to tumor cell apoptosis.
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Nanoscale
·
2025
·
IF 5.1
Sha Liu,Lina Wang,Yupeng Wang,Lina Geng
Delayed healing of post-melanoma-resection wounds is prone to induce tumor recurrence. Therefore, postoperative wound management for tumor resection needs concurrently address anti-cancer activity and wound healing promotion. In this study, a multifunctional micelle-hydrogels (AB@MH) was fabricated by integrating reactive oxygen species (ROS)-responsive nanomicelles, which co-loaded with apigenin and BMS-202, into dodecyl-modified chitosan (DCS) based hydrogel via Schiff base linkages and hydrogen bonding interactions, for post-resection melanoma therapy. This micelle-hydrogel enables ROS-triggered drug release, thereby minimizing systemic toxicity. More importantly, the released apigenin exerts selective cytotoxicity against tumor cells and bacteria while inducing immunogenic cell death (ICD). When combined with co-released BMS-202, the formulation enhances anti-tumor efficacy without harming normal tissue cells. Moreover, the AB@MH is fabricated via a straightforward, crosslinker-free method, ensuring excellent biocompatibility and effective wound healing promotion. In the melanoma resection model, the AB@MH group exhibited marked suppression of tumor recurrence and accelerated wound repair. This work successfully integrates post-resection antitumor therapy and wound healing enhancement, achieving both safety and efficacy in postoperative cancer therapy.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Xue Wang,Yuanyuan Zhang,Yingying Chen,Qing Ma,Hongzhuo Liu,Shi Jin,Guangqi Yan
Diabetic foot ulcers (DFUs) persist due to excessive reactive oxygen species (ROS), infection, and poor angiogenesis. We engineered an injectable guar gum hydrogel (AuCu-Arg/Gel) embedding gold/copper nanozymes (Au@Cu₂(OH)₃Cl– L -Arg) to address these barriers synergistically. The nanozymes display cascade-mimicking peroxidase, superoxide dismutase, and catalase activities to rebalance ROS. In the acidic, bacteria-laden niche, peroxidase-like activity is switched on, generating hydroxyl radicals (•OH) and driving bacterial viability to < 1 %. Concurrently, the ROS-rich milieu triggers nitric oxide (NO) release from L -arginine (2.93 μM in 10 min), upregulating VEGF and neovascularization. Mild near-infrared (NIR) photothermal heating (1.5 W cm⁻², 5 min) increased the apparent POD-like initial rate 1.94-fold vs no-NIR (see Fig. 2 A). without tissue injury. In diabetic rats, AuCu-Arg/Gel plus NIR accelerated wound closure, dampened inflammation, and increased collagen deposition and vascular density. The results confirmed day-12 residual wound areas to 2.1 % (AuCu-Arg/Gel + NIR). This spatiotemporally programmable platform integrates ROS modulation, on-demand antibacterial action, NO gas therapy, and photothermal enhancement for chronic wound management.
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JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Jinjin Liu,Dan Wang,Shuya Wang,Xiaojing Shi,Tingli Xiong,Yebin Lu,Jianbo Yang,Wei Wei,Xuejun Gong,Qiong Huang,Liandong Ji,Kelong Ai
Acute pancreatitis (AP), a potentially fatal disorder driven by macrophage-associated inflammation, involves mitochondrial reactive oxygen species (ROS) overproduction with pancreatic acinar cells (PACs). This ROS surge damages mitochondria, causing mitochondrial DNA (mt-DNA) leakage and PACs apoptosis. Released mt-DNA then activates the pro-inflammatory cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in macrophages, exacerbating disease progression. Critically, while scavenging mitochondrial ROS can halt this cycle, existing mitochondria-targeted drugs fail to penetrate the damaged blood-pancreas barrier (BPB). To overcome this limitation, we developed MTP, a novel dual-targeting nanomedicine synthesized from tannic acid, dopamine, and molybdenum oxides. MTP uniquely achieves dual targeting: actively homing to injured BPB and specifically accumulating within PACs mitochondria. This enables robust mitochondrial ROS scavenging, which protects mitochondrial integrity, reduces mt-DNA release, inhibits PACs apoptosis, and crucially blocks mt-DNA-induced cGAS-STING activation in macrophages, thereby suppressing their pro-inflammatory M1 polarization. By simultaneously interrupting both ROS-mediated PACs damage and macrophage-driven inflammation via this dual-targeting strategy, MTP effectively mitigates AP progression, establishing a breakthrough therapeutic approach.
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Food Bioscience
·
2025
·
IF 5.9
Jingwen Yu,Shilian Zheng,Abdul Mueed,Zeyuan Deng,Hongyan Li
The objectives of this study were to evaluate the antioxidant interactions and underlying mechanisms of the combinations of purple carrot anthocyanins extracts (PCAE) and red papaya carotenoids extracts (RPCE) using tert-butyl hydrogen peroxide (TBHP)-induced human umbilical vein endothelial cells (HUVEC). The results revealed that cyanidin-3-xylosyl (feruloyl glucosyl) galactoside (731.65±2.66 μg/mg) and lycopene (787.50±5.73 μg/mg) were the dominant anthocyanins and carotenoids in purple carrot and papaya, respectively. Cellular antioxidant assays, including cellular antioxidant activity (CAA) and antioxidant enzymes expression, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, showed that in the combinations which contained more hydrophilic PCAE, the combinations would tend to show synergistic effects. When RPCE were in the majority, the combinations would tend to show antagonistic effects. Reverse transcriptase-PCR and western blot analysis revealed the underlying mechanisms of synergistic/antagonistic antioxidant interactions were that they significantly inhibited intracellular ROS generation, exhibiting either synergistic/antagonistic effects on reducing mitochondrial ROS levels, restoring the mitochondrial membrane potential, and inhibiting the activity of the nicotinamide adenine dinucleotide phosphate oxidase 4. Meanwhile, they also reduced cellular ROS level via inhibition of the nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) signaling pathway, to elevate the activities of antioxidant enzymes based on HUVEC cell model. The synergistic/antagonistic antioxidant effects of phytochemical combinations supported their potential as functional food ingredients for cardiovascular diseases prevention.
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