INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Qinqin Zhang,Yipin Zhang,Chenyang Qi,Jie Chen,Haonan Hu,Guitao Tan,Jing Tu
Reactive oxygen species (ROS) play a vital role in wound healing process by fighting against invaded bacteria. However, excess ROS at the wound sites lead to oxidative stress that can trigger deleterious effects, causing cell death, tissue damage and chronic inflammation. Therefore, we fabricated a core–shell structured nanomedicine with antibacterial and antioxidant properties via a facile and green strategy. Specifically, Prussian blue (PB) nanozyme was fabricated and followed by coating a layer of epigallocatechin-3-gallate (EGCG)-derived polymer via polyphenolic condensation reaction and self-assembly process, resulting in PB@EGCG. The introduction of PB core endowed EGCG-based polyphenol nanoparticles with excellent NIR-triggered photothermal properties. Besides, owing to multiple enzyme-mimic activity of PB and potent antioxidant capacity of EGCG-derived polymer, PB@EGCG exhibited a remarkable ROS-scavenging ability, mitigated intracellular ROS level and protected cells from oxidative damage. Under NIR irradiation (808 nm, 1.5 W/cm 2 ), PB@EGCG (50 µg/mL) exerted synergistic EGCG-derived polymer-photothermal antibacterial activity against Gram-negative Escherichia coli ( E. coli ) and Gram-positive Staphylococcus aureus ( S. aureus ). In vivo therapeutic effect was evaluated using a S. aureus -infected rat model indicated PB@EGCG with a prominent bactericidal ability could modulate the inflammatory microenvironment and accelerate wound healing. Overall, this dual-functional nanomedicine provides a promising strategy for efficient antibacterial therapy.
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Regenerative Biomaterials
·
2024
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IF 5.6
Yang Shuaikang,Wang Weiqiang,Xu Yanan,Yuan Yonghui,Hao Shengzhi
Fe-based biodegradable materials have attracted significant attention due to their exceptional mechanical properties and favorable biocompatibility. Currently, research on Fe-based materials mainly focuses on regulating the degradation rate. However, excessive release of Fe ions during material degradation will induce the generation of reactive oxygen species (ROS), leading to oxidative stress and ferroptosis. Therefore, the control of ROS release and the improvement of biocompatibility for Fe-based materials are very important. In this study, new Fe–Zn alloys were prepared by electrodeposition with the intention of using Zn as an antioxidant to reduce oxidative damage during alloy degradation. Initially, the impact of three potential degradation ions (Fe2+, Fe3+, Zn2+) from the Fe–Zn alloy on human endothelial cell (EC) activity and migration ability was investigated. Subsequently, cell adhesion, cell activity, ROS production and DNA damage were assessed at various locations surrounding the alloy. Finally, the influence of different concentrations of Zn2+ in the medium on cell viability and ROS production was evaluated. High levels of ROS exhibited evident toxic effects on ECs and promoted DNA damage. As an antioxidant, Zn2+ effectively reduced ROS production around Fe and improved the cell viability on its surface at a concentration of 0.04 mmol/l. These findings demonstrate that Fe–Zn alloy can attenuate the ROS generated from Fe degradation thereby enhancing cytocompatibility.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Fei Wang,Siwei Li,Xing Wang,Qisen Yang,Jinyou Duan,Yu Yang,Haibo Mu
The progression of severe skin injury healing can be easily impeded by bacterial infections and the resultant overproduction of reactive oxygen species (ROS) within the wound microenvironment. In this study, we developed a multifunctional antibacterial hydrogel by integrating gallium ion-tannic acid and polydopamine particles into gellan gum via a facile heat-cooling process. By harnessing the synergistic effects of polydopamine for short-term photothermal therapy and gallium ion for long-term chemotherapy, the hydrogel obtained shows outstanding antibacterial activities. Sustained release of gallium ion and tannic acid ensures a prolonged sterilization along with ROS-scavenging benefits. Moreover, this hydrogel demonstrates superior cytocompatibility, hemostatic properties, as well as capabilities including promoting cell migration, and adsorption to bacterial cells and toxin. The therapeutic efficacy of the hydrogel was validated using a mouse model of MRSA-induced cutaneous infections. Overall, this work introduces a straightforward yet highly efficient multifunctional hydrogel platform that combines synergetic antibacterial actions, ROS scavenging, and hemostasis to enhance the healing of bacteria-associated wounds.
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Nano Energy
·
2024
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IF 16.8
Junkun Feng,Xiaoyi Liu,Kai Li,Weiwei Zhao,Wenjun Wang,Shaohua Ge,Hong Liu,Jianhua Li
Macrophages are the first line of host defense against bacterial infections and mitochondrial reactive oxygen species (mROS) plays an important role in the bactericidal innate response of macrophages. In this work, we propose the concept of engineering macrophages with artificial mROS generation ability to combat bacterial infection, which is enabled by metal phenolic network-mediated lysosomal escape of piezocatalytic nanoparticles (piezoNPs) and piezotronic effect-enhanced intracellular piezocatalysis. By harvesting ultrasound energy, the engineered macrophages can demonstrate pro-inflammatory phenotype, potent phagocytosis and strong bactericidal activity against Staphylococcus aureus ( S. aureus ). By in situ engineering macrophages at the infection site with targeting ligand-modified piezoNPs, the treatment of S. aureus abscess is further demonstrated. This study reveals the potential of intracellular piezotronic nanocatalysis in enhancing innate immune response of macrophages, providing a non-invasive modulation of macrophages-mediated immunotherapy.
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Bioactive Materials
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2025
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IF 20.3
Haiyan Yao,Emine Sumeyra Turali Emre,Yuan Fan,Jiaolong Wang,Feng Liu,Junchao Wei
Periodontitis is a chronic inflammatory disease characterized by progressive alveolar bone resorption, and excessive reactive oxygen species (ROS) is a key factor to disease progression. Therefore, scavenging ROS to alleviate inflammation and promote bone regeneration are promising strategies to treat periodontitis. In this study, L-arginine (L-Arg) was used to modify mesoporous bioactive glass (MBG), forming L-Arg modified MBG (MBG@L-Arg), which showed effective ROS-scavenging and NO release properties in cells, and realize the protection and restoration of cell's activity in ROS-rich microenvironment. Furthermore, MBG@L-Arg can induce macrophage polarization from M1 to M2 phenotype, and promote the osteogenic differentiation of MC3T3-E1 cells and human periodontal ligament stem cells (hPDLSCs). MBG@L-Arg also regulated anti-inflammatory and antioxidant systems by inhibiting the NF- κ B signaling pathway and activating the Nrf2 signaling pathway. Besides, NO-PKG signaling pathway was also activated, further promoting bone regeneration. The in vivo results demonstrated that MBG@L-Arg can efficiently inhibit inflammation-induced tissue destruction and promote osteogenesis regeneration. The quantitative bone loss in MBG@L-Arg group was 1.03 ± 0.05 mm, significantly lower than that of the periodontitis group (1.47 ± 0.13 mm), implying that MBG@L-Arg can work as multifunctional materials for periodontal tissue regeneration.
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Small
·
2024
·Vol. 20
·期 52
·2407802
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IF 13
Mengyang Li,Yuhang Dong,Yage Shang,Jiaqi Liu,Yunchuan Wang,Dongliang Zhang,Lixia Zhang,Chao Han,Yue Zhang,Kuo Shen,Yaoxiang Yang,Hongtao Wang,Hao Guan,Dahai Hu
Excessive generation of reactive oxygen species (ROS) poses a huge obstacle to the healing process of diabetic wounds, resulting in chronic, non-healing wounds. While numerous anti-ROS therapeutics have been developed, satisfied intra- and extra- cellular ROS homeostasis is hard to be established in diabetic wounds. To address this issue, a nanoparticle via loading metformin and CeO 2 into mesoporous silica (MSN@Met-CeO 2 ) is designed and synthesized, which is then encapsulated within ROS-responsive hydrogel and shaped as microneedles (MNs) for better application in diabetic wounds. Interestingly, a unique metformin-cerium chelate (Ce· 3Metformin) is formed during the synthesis of MSN@Met-CeO 2 MN, which significantly strengthened the inhibitory effect of metformin on mitochondrial complex I. With the presence of Ce· 3Metformin, MSN@Met-CeO 2 MN performed a remarkable effect on intracellular mtROS reduction as well as extracellular ROS elimination, the latter is primarily accomplished through the dissociative CeO 2 in MSN@Met-CeO 2 MN. In the mouse diabetic wound model, MSN@Met-CeO 2 MN exhibited a superior pro-healing effect with accelerated inflammation resolution and enhanced angiogenesis, thus highlighting its significant potential for clinical application
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ACS Biomaterials Science & Engineering
·
2024
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IF 5.4
Wajiha Ahmed,Shifen Li,Min Liang,Yongyuan Kang,Xiaoqing Liu,Changyou Gao
Elevated levels of ROS, bacterial infection, inflammation, and improper regeneration are the factors that need to be addressed simultaneously for achieving effective wound healing without scar formation. This study focuses on the fabrication of electrospun ROS-responsive selenium-containing polyurethane nanofibers incorporating deferoxamine mesylate (Def), indomethacin (Indo), and gold nanorods (AuNRs) as proangiogenesis, anti-inflammatory, and antibacterial agents for synchronized delivery to a full-thickness wound in vivo. The structure of the fabricated nanofibers was analyzed by various techniques. Toxicity was checked by CCK-8 and hemolytic assays. The efficiency of wound healing in vitro was verified by a transwell assay and cell scratch assay. The wound healing efficiency of the nanofibers was assayed in full-thickness wounds in a rat model. The multifunctional nanofibers had a porous structure, enhanced antioxidation, antibacterial activity, and promoted wound healing. They eradicated TNF-α and IL-6, increased IL-10 expression, and revealed the angiogenic potential by increased expression of HIF-1α, VEGF, and CD31.
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BIOMACROMOLECULES
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2024
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IF 5.5
Wali Muhammad,Min Liang,Beiduo Wang,Jieqi Xie,Wajiha Ahmed,Changyou Gao
N-Acetyl cysteine (NAC) is an essential molecule that boosts acute lung injury (ALI) defense via its direct antioxidant capability. Nevertheless, the therapeutic use of NAC is limited due to its poor bioavailability and short half-life. In this study, NAC was grafted to the polyurethane consisting of poly(propylene fumarate), poly(thioketal), and 1,6-hexamethylene diisocyanate (PFTU) to reduce excessive oxidative stress and inflammatory factors in ALI. The NAC-grafted polymer nanoparticles (NPT@NPs) were prepared as a drug delivery system, which could effectively scavenge free radicals and reduce inflammation in vitro. The administration of NPT@NPs exhibited notable efficacy in ameliorating pulmonary edema, attenuating the presence of inflammatory cells, suppressing myeloperoxidase expression, diminishing the levels of pro-inflammatory cytokines, and reversing cell apoptosis in an ALI model induced by lipopolysaccharide (LPS). The NPT@NPs demonstrated significantly better efficacy compared to the free NAC in mitigating the deleterious effects of LPS on pulmonary tissue, thereby providing more effective protection against pulmonary inflammation.
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CHEMISTRY OF MATERIALS
·
2018
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IF 9.89
Ziyang Cao,Yinchu Ma,Chunyang Sun,Zidong Lu,Zeyu Yao,Junxia Wang,Dongdong Li,Youyong Yuan,Xianzhu Yang
Drug delivery systems with remotely controlled drug release capability are rather attractive options for cancer therapy. Herein, a reactive oxygen species (ROS)-sensitive polymeric nanocarrier TK-PPE@NPCe6/DOX was explored to realize remotely controlled drug release by light-activated size shrinkage. The TK-PPE@NPCe6/DOX encapsulating chlorin e6 (Ce6) and doxorubicin (DOX) was self-assembled from an innovative ROS-sensitive polymer TK-PPE with the assistance of an amphiphilic copolymer poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL). Under the 660 nm red light irradiation, ROS generated by the encapsulated Ce6 were capable of cleaving the TK linker in situ, which resulted in the rapid degradation of the TK-PPE@NPCe6/DOX core. Consequently, the size of TK-PPE@NPCe6/DOX shrank from 154 ± 4 nm to 72 ± 3 nm, and such size shrinkage affected further triggered rapid DOX release. As evidenced by both in vitro and in vivo experiments, such ROS-sensitive polymeric nanocarriers with light-induced size shrinkage capability offer remarkable therapeutic effects in cancer treatment. This concept provides new avenues for the development of light-activated drug delivery systems for remotely controlled drug release in vivo.
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BIOORGANIC CHEMISTRY
·
2024
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IF 4.5
Jiawen Yang,Yifan Wu,Qiaoliang Zhu,Xiaojuan Qu,Hongyue Ou,Haixia Liu,Yongqi Wei,Di Ge,Chunlai Lu,Biao Jiang,Xiaoling Song
The c-ros oncogene 1 (ROS1), an oncogenic driver, is known to induce non-small cell lung cancer (NSCLC) when overactivated, particularly through the formation of fusion proteins. Traditional targeted therapies focus on inhibiting ROS1 activity with ROS 1 inhibitors to manage cancer progression. However, a new strategy involving the design of protein degraders offers a more potent approach by completely degrading ROS1 fusion oncoproteins, thereby effectively blocking their kinase activity and enhancing anti-tumour potential. Utilizing PROteolysis-TArgeting Chimera (PROTAC) technology and informed by molecular docking and rational design, we report the first ROS1-specific PROTAC, SIAIS039. This degrader effectively targets multiple ROS1 fusion oncoproteins (CD74-ROS1, SDC4-ROS1 and SLC34A2-ROS1) in engineered Ba/F3 cells and HCC78 cells, demonstrating anti-tumour effects against ROS1 fusion-driven cancer cells. It suppresses cell proliferation, induces cell cycle arrest, and apoptosis, and inhibits clonogenicity. The anti-tumour efficacy of SIAIS039 surpasses two approved drugs, crizotinib and entrectinib, and matches that of the top inhibitors, including lorlatinib and taletrectinib. Mechanistic studies confirm that the degradation induced by 039 requires the participation of ROS1 ligands and E3 ubiquitin ligases, and involves the proteasome and ubiquitination. In addition, 039 exhibited excellent oral bioavailability in a mouse xenograft model, highlighting its potential for clinical application. In conclusion, our study presents a promising and novel therapeutic strategy for ROS1 fusion-positive NSCLC by targeting ROS1 fusion oncoproteins for degradation, laying the foundation for the development of further PROTAC and offering hope for patients with ROS1 fusion-positive NSCLC.
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ACS Omega
·
2024
·
IF 3.7
Qi Tao,Hang Yao,Feifei Wang,Zehao Gu,Xiaofei Yang,Yuchi Zhao,Huan Pang,Dong-An Wang,Hui Chong
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by the disruption of the intestinal epithelial barrier. This study described the synthesis and characterization of CCM-Co-ZIF-8, a novel composite material with enzyme-like activities similar to catalase, peroxidase, and superoxide dismutase. CCM-Co-ZIF-8 demonstrated the ability to scavenge reactive oxygen species that play a critical role in UC pathogenesis. In vitro studies using lipopolysaccharide-induced RAW264.7 cells showed that CCM-Co-ZIF-8 exhibited anti-inflammatory activity by promoting the transition of macrophages from an M1 to an M2 phenotype. In vivo experiments using a mouse model of UC demonstrated that CCM-Co-ZIF-8 suppressed the expression of proinflammatory cytokines. These findings suggested that CCM-Co-ZIF-8 might hold promise as a therapeutic strategy for the treatment of UC.
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Nano Today
·
2025
·
IF 10.9
Zhiwen Wang,Yue Xie,Mingcun Hu,Min Yang,Xingjian Zou,Chun Zhang
Effective countermeasures for acute kidney injury (AKI) remain unsatisfactory. During AKI progression, the timely and appropriate transition of macrophages from pro-inflammatory to anti-inflammatory states is critical for resolving acute inflammation and promoting tissue repair. Timely clearing of excess reactive oxygen species (ROS) and promotion of M2 polarization of macrophages are key determinants of AKI progression. Accordingly, we report an engineered renal-targeting nanozyme constructed from a novel two-dimensional nanomaterial, MXene nanosheets, via surface conjugation of the anticomplement component 5a aptamer (ac5a-Apt) and magnesium ions (Mg 2 + ). After AKI, the engineered nanozyme can not only target the kidneys but also navigates to inflammatory areas under the guidance of the ac5a-Apt, clear excessive ROS, inhibits the C5a-C5aR complement system activation and promote M2 polarization of macrophages. Importantly, after MXene reacts with ROS and degrades, the surface-loaded Mg 2+ is released, further suppressing the MAPK/ NF-κB signaling pathway to achieve sequential therapy. The engineered renal-targeting nanozyme offers a novel strategy based on ROS clearance and immune modulation for sequential AKI treatment.
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