ACS Applied Nano Materials
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2024
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IF 5.3
Fanjia Dai,Fengjiao Chen,Jiaying Zhang,Xianwu Chen,Hongze Liang,Zhenjiang Liang,Shun Zhang,Hui Tan,Lingling Zhao
The tumor microenvironment is distinguished from normal tissues, such as the acidic microenvironment, elevated reactive oxygen species (ROS) levels, and overexpressed specific receptors on the cell surface. According to these unique hallmarks of cancer, stimulus-responsive drug carriers can be designed for targeted anticancer drug delivery and specific drug release in tumor tissues. Herein, a folate-modified pH/ROS dual-responsive polymeric micellar nanosystem was developed for the targeted delivery of doxorubicin (DOX). The drug release profile suggested a sustained drug release from the polymeric micelles and an accelerated drug release at lower pH and higher ROS levels. The cellular uptake assay indicated that the polymeric micelles were internalized by HepG2 cells and that the cellular uptake of micelles can be enhanced by folate modification through a receptor-mediated endocytosis pathway. Furthermore, the folate-modified pH/ROS dual-responsive polymeric micellar nanocarriers demonstrated enhanced inhibition on the migration of HepG2 cells in the cell scratch test and showed improved suppression on the proliferation of HepG2 cells and a lower IC50 than the nonfolate micelles in the cell viability test, indicating the desirable in vitro anticancer efficiency of the nanosystem.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Weitao Hu,Guilan Chen,Wenbin Yuan,Chen Guo,Fasheng Liu,Shouhua Zhang,Zigang Cao
Iprodione is an effective and broad-spectrum fungicide commonly used for early disease control in fruit trees and vegetables. Due to rainfall, iprodione often finds its way into water bodies, posing toxicity risks to non-target organisms and potentially entering the human food chain. However, there is limited information available regarding the developmental toxicity of iprodione specifically on the liver in existing literature. In this study, we employed larval and adult zebrafish as models to investigate the toxicity of iprodione. Our findings revealed that iprodione exposure led to yolk sac edema and increased mortality in zebrafish. Notably, iprodione exhibited specific effects on zebrafish liver development. Additionally, zebrafish exposed to iprodione experienced an overload of reactive oxygen species, resulting in the upregulation of p53 gene expression. This, in turn, triggered hepatocyte apoptosis and disrupted carbohydrate/lipid metabolism as well as energy demand systems. These results demonstrated the substantial impact of iprodione on zebrafish liver development and function. Furthermore, the application of astaxanthin (an antioxidant) and p53 morpholino partially mitigated the liver toxicity caused by iprodione. To summarize, iprodione induces apoptosis through the upregulation of p53 mediated by oxidative stress signals, leading to liver toxicity in zebrafish. Our study highlights that exposure to iprodione can result in hepatotoxicity in zebrafish, and it may potentially pose toxicity risks to other aquatic organisms and even humans.
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Materials Today Bio
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2025
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IF 10.2
Chang Liu,Rui Zhou,Baiqiao Chen,Xinran Yan,Lei Guo,Yixin Tang,Xu Zuo,Xiaoping Guo,Haiyang Yu,Jie Chen,Zhaopei Guo,Fang Wang,Caina Xu
The pathogenesis of acute lung injury (ALI) is characterized by an uncontrolled inflammatory response, marked by excessive production of reactive oxygen species (ROS) and the infiltration of inflammatory cells, particularly macrophages, which play a pivotal role in disease progression. The synergistic effect of ROS scavenging and macrophage repolarization provides a promising strategy for effective ALI treatment. Herein, we developed a novel type of self-assembling nanomicelles, which were composed of poly-L-glutamic acid (PLG) and 4-Hydroxymethyl phenylboronic acid (PBA). The nanomicelles (PPDex micelles) had a high drug-loading capacity for dexamethasone (Dex) based on boronic ester bonds, which exhibited reversible cleavage under inflammatory conditions characterized by elevated levels of ROS or decreased pH values. These PPDex micelles revealed rapid drug-responsive release behavior in the inflammatory environment, and in vivo studies demonstrated their efficacy in modulating cytokines, inhibiting oxidative stress, and promoting macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, which ultimately suppressed the progression of ALI. Moreover, the PPDex micelles had the effective ability to effectively suppress the NF-кB and ROS/NLRP3 inflammatory pathways. Therefore, this study presented a novel and potent therapeutic strategy for ALI treatment, which could promote the clinical application of polymer nanomicelles in the treatment of ALI.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Xiaowei Liu,Ningning Diao,Shiqing Song,Wenxin Wang,Min Cao,Weili Yang,Chunjing Guo,Daquan Chen
During the pathogenesis of rheumatoid arthritis, inflammatory cells usually infiltrate synovial tissues, notably, M1-type macrophages, whose redox imbalance leads to the degradation of joint structures and deterioration of function. Natural active products play a vital role in immune modulation and antioxidants. In this study, we constructed a ROS-responsive nanoparticle called FTL@SIN, which consists of fucoidan (Fuc) and luteolin (Lut) connected by a ROS-responsive bond, Thioketal (TK), and encapsulated with an anti-rheumatic drug, Sinomenine (SIN), for synergistic anti-inflammatory effects. The FTL@SIN is then dispersed in high molecular weight Fuc-fabricated dissolvable microneedles (FTL@SIN MNs) for local administration. Therapy of FTL@SIN MNs afforded a significant decrease in macrophage inflammation while decreasing key pro-inflammatory cytokines and repolarizing M1 type to M2 type, thereby ameliorating synovial inflammation, and promoting cartilage repair. Additionally, our investigations have revealed that Fucoidan (Fuc) demonstrates synergistic effects, exhibiting superior mechanical strength and enhanced physical stability when compared to microneedles formulated solely with hyaluronic acid. This study combines nanomedicine with traditional Chinese medicine, a novel drug delivery strategy that presents a promising avenue for therapeutic intervention in rheumatoid arthritis.
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ACS Applied Materials & Interfaces
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2024
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IF 8.3
Yue Yu,Ziying You,Xin Li,Feng Lou,Ding Xiong,Ling Ye,Zhenming Wang
Injectable antibacterial and osteoinductive hydrogels have received considerable attention for promoting bone regeneration owing to their versatile functionalities. However, a current hydrogel with antibacterial, osteoinductive, and antioxidant properties by a facile method for periodontitis treatment is still missing. To overcome this issue, we designed an injectable hydrogel system (GPM) composed of gelatin, Ti3C2Tx MXene nanosheets, and poly-l-lysine using a simple enzymatic cross-linking technique. Physicochemical characterization demonstrated that the GPM hydrogel matrix exhibited excellent stability, moderate tissue adhesion ability, and good mechanical behavior. The GPM hydrogels significantly inhibited the growth of Porphyromonas gingivalis, scavenged reactive oxygen species, attenuated inflammatory responses, and enhanced bone tissue regeneration. Intriguingly, the arrangement of the junctional epithelium, alveolar bone volume, and alveolar bone height in the GPM-treated periodontal disease group recovered to that of the healthy group. Therefore, our injectable hydrogel system with versatile functions may serve as an excellent tissue scaffold for the treatment of periodontitis.
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CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Zhencheng Sun,Jiaxin Wang,Minghui Xiao,Kaiyu Wu,Cheng Wang,Hao Fu,Shuyi Lv,Linqi Shi,Chunlei Zhu
Type-I photodynamic therapy (PDT), valued for its reduced oxygen requirement, generates highly cytotoxic •OH radicals. However, conventional strategies for developing type-I photosensitizers (PSs) are complex and involve intricate organic synthesis. Herein, we present a novel strategy to alter the generation of reactive oxygen species (ROS) by simply manipulating the twisting degree of donor–acceptor (D−A) type aggregation-induced emission (AIE) PSs. Specifically, natural saturated fatty acids are employed to modulate the twisting state of AIE PSs, with higher doping ratios yielding more twisted structures and increased type-I ROS generation. In contrast, fatty acids with higher crystallinity promote planar structures and type-II ROS generation. Theoretical calculations suggest that AIE PSs with highly twisted structures lead to a prominent reduction in Δ E ST and effective separation of electron−hole pairs, thereby favoring efficient intersystem crossing and charge transfer. The PDT system primarily driven by type-I ROS exhibits efficient bactericidal activity against clinically drug-resistant bacteria, which remarkably accelerates the recovery of bacteria-infected wounds in mice. This study demonstrates the first example of modulating ROS generation type by manipulating the twisting degree of D−A type AIE PSs, eliminating the need for intricate molecular design and organic synthesis. The proposed strategy opens up new avenues for advancing PDT applications.
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Advanced Healthcare Materials
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2024
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IF 10
Meng Sun,Nan Hu,Yangyang Gao,Nan Lv,Xiaohong Fu,Yafeng Li,Shaodong Zhai,Ruiping Zhang
Ischemia-induced myocardial injury has become a serious threat to human health, and its treatment remains a challenge. The occurrence of ischemic events leads to a burst release of reactive oxygen species (ROS), which triggers extensive oxidative damage and leads to dysfunctional autophagy, making it difficult for cells to maintain homeostasis. Antioxidants and modulation of autophagy have thus become promising strategies for the treatment of ischemic myocardial injury. This study proposes an antioxidant-activated autophagy therapeutic regimen based on combining melanin (Mel), an excellent antioxidant with metformin mimetic ploymetformin via electrostatic interactions, to obtain a nanocomplex (Met-Mel). The nanocomplex is finally encapsulated with platelet membranes (PMN) to construct a biomimetic nanoparticle (PMN@Met-Mel) capable of targeting injured myocardium. The prepared PMN@Met-Mel has good Mel loading capacity and optimal biosafety. It exhibits excellent antioxidant activity and autophagy activation, rapidly restoring mitochondrial function. Moreover, RNA sequencing (RNA-seq) analysis reveals that PMN@Met-Mel operates mechanistically by triggering the activation of the autophagy pathway. Subsequent in vivo experiments showcase promising cardioprotective effects of these nanoparticles. These discoveries present a newly devised nanoplatform with promising potential for the effective treatment of myocardial infarction.
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FREE RADICAL BIOLOGY AND MEDICINE
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2024
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IF 7.1
Haoyu Wang,Junqi Zhao,Shiliang Ji,Tingjun Liu,Zhisheng Chen,Zhen Huang,Yuhui Zang,Jiangning Chen,Junfeng Zhang,Zhi Ding
Alcoholic liver disease (ALD) is a common chronic redox disease caused by increased alcohol consumption. Abstinence is a major challenge for people with alcohol dependence, and approved drugs have limited efficacy. Therefore, this study aimed to explore a new treatment strategy for ALD using ferroferric oxide endohedral fullerenol (Fe 3 O 4 @C 60 (OH) n ) in combination with static magnetic and electric fields (sBE). The primary hepatocytes of 8–9-week-old female BALB/c mice were used to evaluate the efficacy of the proposed combination treatment. A mouse chronic binge ethanol feeding model was established to determine the alleviatory effect of Fe 3 O 4 @C 60 (OH) n on liver injury under sBE exposure. Furthermore, the ability of Fe 3 O 4 @C 60 (OH) n to eliminate •OH was evaluated. Alcohol-induced hepatocyte and mitochondrial damage were reversed in vitro . Additionally, the combination therapy reduced liver damage, alleviated oxidative stress by improving antioxidant levels, and effectively inhibited liver lipid accumulation in animal experiments. Here, we used a combination of magnetic derivatives of fullerenol and sBE to further improve the ROS clearance rate, thereby alleviating ALD. The developed combination treatment may effectively improve alcohol-induced liver damage and maintain redox balance without apparent toxicity, thereby enhancing therapy aimed at ALD and other redox diseases.
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Frontiers in Pharmacology
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2024
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IF 4.4
Hao Ying,Liu Tailuo,Zhou Hao,Xu Runhao,Li Ka,Chen Mao,Chen Yuwen
Introduction: The synergistic treatment of chemotherapy and photodynamic therapy (PDT) has remarkable potential in cancer therapy. However, challenges remain, such as unstable chemotherapeutic drug release, suboptimal targeting, and reduced efficacy of PDT under hypoxic conditions commonly found in solid tumors.Methods: To address these issues, we use camptothecin (CPT) and pheophorbide a (Pa) incorporated through the functional thioketal, which serves as the reactive oxygen species (ROS)-responsive trigger, to construct a ROS-responsive prodrug (CPT-TK-Pa). Subsequently, we co-loaded it with a platinum nanozyme (PtNP) in distearylphosphatidylethanolamine–polyethylene glycol (DSPE–PEG) to obtain the ROS-responsive prodrug nanoparticle (CPT-TK-Pa/Pt NP).Results and Discussion: Specifically, the incorporated PtNP within CPT-TK-Pa/Pt NP positively catalyzes the conversion of hydrogen peroxide (H2O2) to oxygen, thereby ameliorating the hypoxic state of the tumor. This enhanced oxygen generation could replenish the oxygen that is consumed by Pa during 660 nm exposure, enabling controlled CPT release and amplifying the photodynamic response. In vitro investigations reveal the potency of CPT-TK-Pa/Pt NPs in inhibiting colon tumor cells. Given its ROS-responsive release mechanism and enhanced PDT efficacy, CPT-TK-Pa/Pt NP has the potential to be a promising candidate for cancer therapy.
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JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Penghao Zhen,Qiaochu Jiang,Fuchao Yu,Xuan Xu,Qin Wei,Xiaoyang Liu,Xianbao Sun,Gaolin Liang,Jiayi Tong
Treatment of myocardial ischemia-reperfusion (MI/R) injury still faces the lack of clinically approved drugs. Apelin-13 is a highly promising drug candidate of MI/R injury, but hampered by its extremely short half-life in plasma. This calls for efficient and smart delivering system for Apelin-13 delivery, but has not been reported. Herein, a reactive oxygen species (ROS)-responsive hydrogelator YFF-TK-FFY is designed, which co-assembles with Apelin-13 to form the peptide hydrogel Apelin-13@Gel TK . This hydrogel responds to ROS at varying levels in the surrounding environment of MI/R and releases Apelin-13 at different rates. In an MI/R injury mouse model, Apelin-13@Gel TK rapidly releases Apelin-13 in response to the high ROS in the core area of MI/R injury, efficiently reducing cardiomyocyte apoptosis within three days. In the ROS-low border zone, Apelin-13@Gel TK provides a slow and sustained release of Apelin-13, promoting angiogenesis and lymphatic remodeling, and facilitating the resolution of inflammation in the later repair stage after MI/R injury. By offering a spatiotemporally controlled drug release in response to ROS gradients in the MI/R microenvironment, this smart hydrogel presents a promising therapeutic strategy for effective treatment of MI/R injury.
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BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Rongrong Luo,Jingjing Su,Wenying Zhang,Wenguang Huang,Qianqian Zhou,Pengchao Sun,Yongxing Zhao
Rheumatoid arthritis (RA) is characterized by high level of reactive oxygen species (ROS) and proinflammatory cytokines, which facilitate the activation of the inflammatory signaling such as NF-κB pathway and exacerbate the development of inflammation. Herein, we designed a nanodrug by encapsulating the NO donor S-nitrosoglutathione (GSNO) into an emulsion and coating the surface with a polydopamine (PDA) layer to yield GSNO@PDA, which simultaneously scavenged the extra ROS and suppressed NF-κB signaling for potent RA treatment. To enhance the cellular uptake and NO generation efficiency, dextran sulfate (DS) and Cu 2+ were anchored on the surface of GSNO@PDA to obtain the final formulation GSNO@PDA@DS. Our results demonstrated that GSNO@PDA@DS were successfully prepared and the modification of DS effectively boosted the cellular uptake of GSNO@PDA@DS. Moreover, GSNO@PDA@DS lowered cellular ROS and elevated intracellular NO, resulting in a decrease of M1 phenotype, inhibition of NF-κB pathway and down-regulation of proinflammatory cytokine tumor necrosis factor-α (TNF-α). Further in vivo studies confirmed that GSNO@PDA@DS significantly relieved symptoms and bone erosion by regulating the microenvironment of RA, highlighting the potential of GSNO@PDA@DS for RA therapy through ROS scavenging and NO-mediated suppression of inflammatory signaling.
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Materials Science and Engineering B-Advanced Functional Solid-State Materials
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2025
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IF 4.6
Yan Li,Ming Shen,Jing Kong
Although the antibacterial properties of ZnO nanoparticles have been widely studied for potential biomedical applications, their relatively mild antibacterial activity still limits the clinical application of ZnO-based antibacterial materials. Here, we reported a new method to improve the antibacterial activity and visible light absorption of ZnO nanoparticles by incorporating allicin on the surface. The synthesis was performed through a simple condensation reflux reaction to obtain the designed series of ZnO/Allicin composites. FT-IR, XRD, and TEM analysis proved the structure and composition of the obtained composites. All composites show visible light absorption in the UV–visible diffuse reflectance spectroscopy analysis. Through antibacterial activity tests, the ZnO/allincin-1 % sample showed significantly enhanced activity (2-fold increase) against Staphylococcus aureus after visible light excitation. Antibacterial mechanistic investigations reveal that the composition of allicin with the ZnO nanoparticles not only improves ROS productive ability but also enhances the release of Zn 2+ . Overall, this study provides a practical, convenient, and economic strategy to refine the visible light absorption and antibacterial activity of ZnO without introducing more toxic metal ions. In the meantime, this new nanomaterial could be a good starting point for initiating clinically applicable ZnO nanocomposites.
研究领域:
材料科学
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微生物学
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生物医学工程
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