International Journal of Nanomedicine
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2024
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IF 6.6
Jing Wang,Yanxiang Sang,Weijian Chen,Liang Cheng,Wenxiang Du,Hongjie Zhang,Benyan Zheng,Lei Song,Yuan Hu,Xiaopeng Ma
Introduction As an effective alternative choice to traditional mono-therapy, multifunctional nanoplatforms hold great promise for cancer therapy. Based on the strategies of Fenton-like reactions and reactive oxygen species (ROS)-mediated therapy, black phosphorus (BP) nanoplatform BP@Cu2O@L-Arg (BCL) co-assembly of cuprous oxide (Cu2O) and L-Arginine (L-Arg) nanoparticles was developed and evaluated for synergistic cascade breast cancer therapy.Methods Cu2O particles were generated in situ on the surface of the BP nanosheets, followed by L-Arg incorporation through electrostatic interactions. In vitro ROS/nitric oxide (NO) generation and glutathione (GSH) depletion were evaluated. In vitro and in vivo anti-cancer activity were also assessed. Finally, immune response of BCL under ultrasound was investigated.Results Cu2O was incorporated into BP to exhaust the overexpressed intracellular GSH in cancer cells via the Fenton reaction, thereby decreasing ROS consumption. Apart from being used as biocompatible carriers, BP nanoparticles served as sonosensitizers to produce excessive ROS under ultrasound irradiation. The enhanced ROS accumulation accelerated the oxidation of L-Arg, which further promoted NO generation for gas therapy. In vitro experiments revealed the outstanding therapeutic killing effects of BCL under ultrasound via mechanisms involving GSH deletion and excessive ROS and NO generation. In vivo studies have illustrated that the nanocomplex modified the immune response by promoting macrophage and CD8+ cell infiltration and inhibiting MDSC infiltration.Discussion BCL nanoparticles exhibited multifunctional characteristics for GSH depletion-induced ROS/NO generation, making a new multitherapy strategy for cascade breast cancer therapy.
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Science Advances
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2024
·Vol. 10
·期 38
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IF 11.7
Jianing Li,Tianze Wu,Weidong Wang,Yimin Gong,Mingzhu Lu,Mengmeng Zhang,Wanyue Lu,Yaming Zhou,Yannan Yang
In situ vaccine (ISV) is a versatile and personalized local immunotherapeutic strategy. However, the compromised viability and function of dendritic cells (DCs) in a tumor microenvironment (TME) largely limit the therapeutic efficacy. We designed a hybrid nanoparticle–based ISV, which accomplished superior cancer immunotherapy via simultaneously scavenging reactive oxygen species (ROS) and activating the stimulator of interferon genes (STING) pathway in DCs. This ISV was constructed by encapsulating a chemodrug, SN38, into diselenide bond–bridged organosilica nanoparticles, followed by coating with a Mn2+-based metal phenolic network. We show that this ISV can activate the STING pathway through Mn2+ and SN38 comediated signaling and simultaneously scavenge preexisting H2O2 in the TME and Mn2+-catalyzed •OH by leveraging the antioxidant property of diselenide and polyphenol. This ISV effectively activated DCs and protected them from oxidative damage, leading to remarkable downstream T cell activation and systemic antitumor immunity. This work highlights a nanoparticle design that manipulates DCs in the TME for improving the ISV.
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CHINESE JOURNAL OF CATALYSIS
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2024
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IF 15.7
Meiyun Zhang,Penghua Che,Hong Ma,Xin Liu,Shujing Zhang,Yang Luo,Jie Xu
Clean catalytic oxidation has a broad prospect in the modern chemical engineering and energy chemistry fields. However, unexpected over-oxidation and disruptive degradation are frequently induced by excessive reactive oxygen species (ROS). Herein, we reported a new ROS-free approach to effectively drive O 2 to be activated into highly reactive surface peroxo species through enzyme-mimicking mechanism. Benefiting from the dual-metal synergy effect between Cu and Co active sites, ROS (H 2 O 2 and OH • ) is generated in situ while further scavenged completely into surface peroxo species, which gives rise to very high selectivity and extremely high carbon balance. For example, the CuCo/N-C catalyst affords >99.8% conversion and 94.5% selectivity to 2,5-furanedicarboxylic acid at 25 °C for 6 h in the aerobic oxidation of biomass platform 5-hydroxymethylfurfural. Moreover, it achieved exceptional performance in the oxidation of a variety of hydroxyl compounds to organic acids with high yields (89.9%–99.5%) at a mild temperature (25–40 °C). This exploration introduces an innovative clue for emulating enzyme catalysts, thereby enriching our comprehension and advancement of biologically inspired catalytic oxidations.
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JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Hongxin Cai,Yu Zhang,Jingyu Wang,Yufeng Deng,Jiangyuan Liu,Zhiguo Wu,Dejian Cao,Zhiying Song,Lele Wang,Baogang Xie
Ethnopharmacological relevance Liuwei dihuang pills is a famous Traditional Chinese Medicine with various anti-cancer properties. Over 50 pharmaceutical manufacturers produce Liuwei dihuang pills in China and an estimated millions of people around the world orally take it every day. D-glucaro-1,4-lactone (1,4-GL) was quantified to be about 12.0 mg/g in Liuwei dihuang pills and a primary bioactive component of it inhibiting the activity of β-glucuronidase in vivo. 1,4-GL can prevent and effectively inhibit various types of cancer. However, its exact mechanism of action remains unknown. The study would justify the traditional usage of Liuwei dihuang pills against cancers. Aim of the study 1,4-GL, a bioactive ingredient derived from Liuwei dihuang pills, a famous Traditional Chinese Medicine, could delay the progression of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. The mechanism underpinning the effect, however, remains poorly understood. Materials and methods Healthy and HCC rats were treated with or without 1,4-GL (40.0 mg/kg) and 1 HNMR-based metabonomic analysis was employed. 10 metabolites in uric acid pathway were quantitatively determined by UPLC-MS/MS. The expression of xanthine dehydrogenase (XDH), SLC2A9 mRNA, and SLC2A9 protein was determined using RT-qPCR and Western Blot. The effect of 1,4-GL on HCC-LM3 cells was verified in vitro. The alterations of ROS activity, SLC2A9 and XDH gene levels were observed in NCTC-1469 cells induced by lipopolysaccharide (LPS) after 1,4-GL treatment. Results After the intervention of 1,4-GL, improved pathological morphology, liver lesions in HCC rats was observed with restored serum levels of AFP, AST, ALP, γ-GGT and Fisher's ratio. Hepatic metabonomics revealed that puring metabolism were significantly regulated by 1,4-GL in HCC rats. Uric acid, xanthine and hypoxanthine levels were quantified by UPLC-MS/MS and found to be nearly restored to control levels after 1,4-GL treatment in HCC rats. Changes in xanthine oxidase activity, XDH mRNA expression, and SLC2A9 mRNA and protein expression were also reversed. 1,4-GL treatment in LM3 HCC cells were consistent with the results in vivo. Furthermore, oxidative stress indicators such as T-SOD, GSH, CAT and MDA in serum and liver were improved after HCC rats treated with 1,4-GL. In vitro, 1,4-GL was observed to reduce lipopolysaccharide-induced ROS levels in NCTC-1469 cells with enhanced mRNA and protein expression of SLC2A9 and decreased mRNA level of XDH. Conclusion The protective effects of 1,4-GL against DEN-induced HCC by reducing uric acid and ROS levels due to down-regulation of uric acid production and up-regulation of SLC2A9 expressions. 1,4-GL may represent a novel treatment that improves recovery from HCC by targeting uric acid-ROS pathway.
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ACS Biomaterials Science & Engineering
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2025
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IF 5.5
Yi Yu,Mingjin Zhang,Jing Li,Zhengyuan Liu,Liang Lyu,Yujia Xiao,Gengchen Yang,Jiayi Liu,Qirui Wang,Xiaoyang Ding,Ting Zhang,Yuguang Wang,Xing Wang,Tingting Yu,Dawei Liu
Diabetes mellitus is a global health threat, with chronic wounds, including oral mucosal wounds, being a severe complication. These wounds are characterized by delayed healing and increased inflammation due to hyperglycemia, affecting patients’ quality of life. Current treatments for oral mucosal wounds cannot offer sustained management of these injuries in diabetic patients. Here, a glucose/ROS dual-responsive hydrogel incorporating sitagliptin was developed for the treatment of diabetic oral mucosal wounds. After chemical modification of tetra-armed poly(ethylene glycol) succinimidyl glutarate (tetra-PEG-SG) by dopamine (DA) and tetra-armed poly(ethylene glycol) amine (tetra-PEG-NH2) by phenylboronic acid (PBA), the resulting hydrogel was capable of rapid gelation, robust tissue adhesion, self-healing, antioxidant capacity, and dual response to glucose and reactive oxygen species (ROS), enabling the feasible injection and stable adherence in the moist oral environment while ensuring sustained therapeutic sitagliptin release. In vivo experiments on oral mucosal defects in diabetic mice revealed that the sitagliptin-loaded hydrogel could effectively reduce inflammation and promote wound healing. Collectively, this finding identifies a potential wound dressing as a therapeutic strategy for diabetic oral mucosal wounds.
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Acta Biomaterialia
·
2024
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IF 9.4
Yin Zheng,Mingyue Wang,Xinge Zhang,Zhongming Wu,Ling Gao
Delayed wound healing in patients with diabetes remains a major health challenge worldwide. Uncontrolled bacterial infection leads to excessive production of reactive oxygen species (ROS) and persistent inflammatory responses, which seriously hinder conventional physiological healing processes after injury. Biofilms, as protective barriers for bacteria, pose a critical obstacle to effective bacterial eradication. Herein, an innovative therapeutic nanoplatform with in situ antibacterial and antioxidant properties is developed for enhancing infected diabetic wound healing. The enrichment of phenylboronic acid (PBA) moieties on the nanoplatform enhances biofilm penetration, actively anchors and aggregates the enclosed bacteria through the "multivalent effect", with an anchoring efficiency as high as 80%. Additionally, glycine moieties on the nanoplatform ensure spatial extensibility by charge repulsion, enabling targeted antibiotic release around bacteria. This precise antibacterial effect increases the bactericidal activities of the nanoplatform against S. aureus or P. aeruginosa by 25% and 22% respectively, effectively eliminating the bacteria and dispersing the biofilms. Furthermore, 3,4-dihydropyrimidin-2(1H)-one (DHPM) moieties act as ROS scavengers that alleviate oxidative stress and inflammatory responses, promoting tissue repair progression into the proliferative phase characterized by increased extracellular matrix deposition, angiogenesis, and granulation tissue formation, ultimately accelerating diabetic wound healing. Overall, this work presents an innovative bacterial response strategy for achieving in situ antibacterial and antioxidant effects in infected tissues and provides a promising therapeutic approach for treating infected diabetic wounds. Statement of significance : Infected diabetic wound management remains a major world health issue. Severe bacterial infection leads to excessive oxidative stress and persistent inflammatory response, which seriously hinders the wound healing process. As a protective barrier for bacteria, biofilms are a key obstacle to effective bacterial clearance. This study provides a bacteria-responsive nanoplatform for the healing of infected diabetic wounds. The nanoplatform not only exhibits improved biofilm penetration but also actively anchors the enclosed bacteria and enables targeted antibiotic release to disperse the biofilm. The DHPM moieties of the nanoplatform act as ROS scavengers which could alleviate inflammatory responses, promote tissue repair progression into the proliferative phase, and ultimately accelerate diabetic wound repair.
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CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Jun Tao,Hui Deng,Zhengnan Li,Liping Cao,Yanfei Rao,Zhanhai Yin
The progression and severity of osteoarthritis (OA) are significantly associated with intra-articular synovitis, with the imbalance of M1/M2 macrophages serving as a critical driving factor in the pathogenesis of synovitis. In this study, we developed macrophage-targeted nanomicelles capable of scavenging reactive oxygen species (ROS) and releasing hydrogen sulfide (H 2 S). These nanomicelles were encapsulated within injectable methacrylate gelatin (GelMA) porous hydrogel microspheres, thereby creating a new H 2 S gas therapy platform for the treatment of osteoarthritis. In vitro experiments demonstrated that GelMA@FPLBD actively targeted macrophages, efficiently removed ROS, and gradually released H 2 S. This process inhibited the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in activated macrophages, thereby suppressing M1 polarization and promoting M2 polarization, resulting in significant anti-inflammatory effects. In vivo experiments utilizing a destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) rat model further revealed the anti-inflammatory and cartilage-protective properties of GelMA@FPLBD, effectively mitigating the progression of OA. Therefore, this study indicates that GelMA@FPLBD, functioning as a H 2 S gas therapy platform, holds significant promise for the treatment of osteoarthritis (OA).
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yu Liu,Meng Zhu,Jinzhao Ou,KeJia Li,Xiaoyan Ju,Ye Tian,Zhongwei Niu
Oxidative stress caused by excessive reactive oxygen species (ROS) accumulation significantly hinders wound healing in patients with diabetes. Scavenging ROS and reducing inflammation are crucial for rapid healing. In this work, a multi-responsive sodium hyaluronate (HA)/tannic acid (TA) hydrogel was developed based on boronate ester bonds. Sodium hyaluronate with 3-aminophenyl boronic acid modification (HA-APBA) was mixed and crosslinked with TA to form HA-APBA/TA hydrogels. These hydrogels are injectable, self-healing, and biocompatible. The HA-APBA/TA hydrogels could release free TA through the collapse of the structure at low pH, high H 2 O 2 concentration, and high glucose concentration, thus possessing good ROS scavenging ability. In full-thickness skin wounds of db/db mice, the HA-APBA/TA hydrogels promoted wound healing, collagen deposition, and significant angiogenesis. Furthermore, they have been shown to effectively reduce the levels of inflammatory factors in wounds and lower the expression of CD86, a pro-inflammatory macrophage surface marker. This resulted in a more effective transition of wound healing from the inflammatory phase to the proliferative phase. This study provides an optional strategy for alleviating oxidative stress and controlling excessive inflammation, thereby promoting diabetic wound healing.
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International Journal of Nanomedicine
·
2024
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IF 6.6
Ye Ming,Xinyi He,Zhenxing Zhao,Xuehuan Meng,Ye Zhu,Hao Tan,Guoyin Yang,Yun Hu,Leilei Zheng
Purpose Oxidative stress and mitochondrial dysfunction are potential contributors to the compromised tissue regeneration capacity of alveolar bone in diabetic patients. Berberine, an active plant alkaloid, exhibits multiple pharmacological effects including antioxidation, blood glucose- and blood lipid-lowering properties. However, it remains uncertain whether berberine can improve impaired osteogenesis in type 2 diabetes mellitus (T2DM), and its poor solubility and oral bioavailability also constrain its applications in bone regeneration. Thus, our study aimed to probe the effects of berberine on bone marrow stem cells (BMSCs) in a diabetic microenvironment, with a greater emphasis on developing a suitable nano-delivery system for berberine and assessing its capability to repair diabetic alveolar bone defects.Methods Firstly, BMSCs were exposed to berberine within a high glucose and palmitate (HG+PA) environment. Reactive oxygen species levels, mitochondrial membrane potential, ATP generation, cell apoptosis, and osteogenic potential were subsequently assessed. Next, we explored the regulatory mechanism of autophagy flux in the positive effects of berberine. Furthermore, a nanocarrier based on emulsion electrospinning for sustained local delivery of berberine (Ber@SF/PCL) was established. We assessed its capacity to enhance bone healing in the alveolar bone defect of T2DM rats through micro-computed tomography and histology analysis.Results Berberine treatment could inhibit reactive oxygen species overproduction, mitochondrial dysfunction, apoptosis, and improve osteogenesis differentiation by restoring autophagy flux under HG+PA conditions. Notably, Ber@SF/PCL electrospun nanofibrous membrane with excellent physicochemical properties and good biological safety had the potential to promote alveolar bone remodeling in T2DM rats.Conclusion Our study shed new lights into the protective role of berberine on BMSCs under T2DM microenvironment. Furthermore, berberine-loaded composite electrospun membrane may serve as a promising approach for regenerating alveolar bone in diabetic patients.
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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2024
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IF 4.4
Kangyuan Hu,Xiuhua Li,Zhaodan Tan,Yan Shi
Ovarian cancer is the most common malignant tumor in women. Shikonin (SHK), an herbal extract from Chinese medicine, shows promise in treating ovarian cancer by inducing reactive oxygen species (ROS). However, its clinical use is limited by poor tumor targeting and low bioavailability, and its therapeutic potential is further compromised by the elevated levels of antioxidants such as glutathione (GSH) within tumor cells. In this study, a novel formulation of ROS-responsive micelles loaded with SHK was developed using hyaluronic acid-phenylboronic acid pinacol ester conjugation (HA-PBAP) for targeted therapy of ovarian cancer through disruption of intracellular redox homeostasis. The SHK@HA-PBAP exhibits targeted delivery to ovarian cancer cells through the interaction between HA and CD44 receptors. Upon internalization by cancer cells, the high levels of intracellular ROS triggered the degradation of SHK@HA-PBAP and simultaneously released SHK and generated GSH scavenger quinone methide (QM). The SHK and QM released from the SHK@HA-PBAP effectively induce the production of ROS and deplete intracellular GSH, leading to the disruption of intracellular redox homeostasis and subsequent induction of cell death. These characteristics collectively inhibit the growth of ovarian cancer. In vitro and in vivo studies have demonstrated that SHK@HA-PBAP micelles exhibit superior antitumor efficacy compared to free SHK in both A2780 cells and A2780 tumor-bearing mice. The ROS-responsive SHK@HA-PBA presents a promising therapeutic approach for the treatment of ovarian cancer.
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JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-23
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IF 10.6
Zhao Pei,Hu Hua-Zhong,Chen Xiao-Tong,Jiang Qi-Yun,Yu Xue-Zhao,Cen Xiao-Lin,Lin Shi-Qing,Mai Sui-qing,Pang Wei-lin,Chen Jin-Xiang,Zhang Qun
Background Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. Results In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H 2 O 2 ) to produce O 2 , which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine’s capacity for UA degradation, O 2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. Conclusions The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout. Graphical Abstract
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Ruideng Wang,Xi He,Shilong Su,Jinwu Bai,Haifeng Liu,Fang Zhou
The repair of diabetic bone defects is still filled with enormous challenges. Excessive reactive oxygen species (ROS) are regenerated in diabetic bone defect sites which is harmful to bone regeneration. Therefore, it's to a good strategy to scavenge the excess ROS to provide a friendly environment for diabetic bone defects repair. Herein, a novel composite hydrogel with ROS-scavenging and osteogenic ability is constructed. This methacrylated silk fibroin based composite hydrogel is capable of releasing tannin acid and inorganic ion, which can reduce oxidative stress, restore homeostasis and enhance osteogenesis. In vitro results indicated that the composite hydrogel could promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under oxidative stress condition. Furthermore, in vivo results suggested that it can significantly promote bone regeneration in diabetic bone defects. In conclusion, this study provides critical insight into the biological mechanism and potential therapy for diabetic bone regeneration.
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