Biomaterials Advances
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2022
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IF 0
Xin Mu,Yulei Chang,Ying Bao,Anni Cui,Xiahua Zhong,Griffin B. Cooper,Anika Guo,Guiye Shan
Photodynamic therapy (PDT) efficiency is directly affected by the reactive oxygen species (ROS) generated by photosensitizers. However, ROSs' ultrashort life span and limited diffusion distance restrict the PDT efficiency. Therefore, it is important to control the delivery strategy of photosensitizers for PDT treatment. Herein, the core-satellite nanoreactors were fabricated with oxygen generation and ROS diffusion properties. The hollow CuS encapsulating horseradish peroxidase (HRP) was combined with the cationic photosensitizers (PEI-Ce6). The unique photosensitizers delivery strategy makes the nanoreactors achieve ROS diffusion-enhanced PDT effect. First, HRP in “core” (HRP@CuS) can decompose hydrogen peroxide (H 2 O 2 ) to O 2 , increasing O 2 levels on the surface of the nanoreactor. Second, the Ce6 molecules covalent-linked with PEI are uniformly dispersed on the surface of CuS as a “satellite”, avoiding Ce6 aggregation and causing more Ce6 molecules be activated to produce more 1 O 2 . Due to the Ce6 was on the surface of the CuS nanocages, the generated ROS may ensure a larger diffusion range. Meanwhile, the inherently CuS nanocages exhibit photothermal and photoacoustic (PA) effect. The photothermal effect further enhances the ROS diffusion. Under the guidance of PA imaging, nanoreactors exhibit highly efficient hypoxic tumor ablation via photodynamic and photothermal effect. Overall, the core-satellite nanoreactors provide an effective strategy for tumor therapy, further promoting the research of photosensitizers delivery.
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MATERIALS & DESIGN
·
2023
·
IF 8.4
Haiting Xu,Linxin Dai,Wenbiao Nie,Ruifeng Luo,Xiulan Pu,Lingling Dong,Qiyan Chen,Shanshan Qi,Xiaoqin Han,Jieshu You,Jinming Zhang,Fei Gao
Cyclodextrins (CDs) have been applied widely as an oral micro-nano drug delivery material for the treatment of ulcerative colitis (UC) because of their stability around the stomach. However, the further application of CDs is hindered due to their inherent poor targeting and controlled release properties. In this study, CD-supramolecular nanoparticles ( [email protected] ) were developed based on the structural characteristics of CDs (e.g., multi-group modifiability and hydrophobic cavity) to encapsulate rhein (RH) for oral delivery against UC. The [email protected] showed an average size of 154.70 ± 1.80 nm and exhibited high encapsulation efficiency (95.55 ± 2.37 %). When incubated in simulated gastric fluid for 2 h, [email protected] only released 20.3 ± 0.47 % RH due to the protection of supramolecular effects of CDs. However, RH was rapidly released from [email protected] (released 66.3 ± 2.50 %) after H 2 O 2 was treated with the assistance of the ROS-sensitive properties. Moreover, [email protected] were taken up by macrophages in 1.5 times higher amounts than preparations which did not have CD44-targeted effects. Notably, the results showed that [email protected] with an accurate on-demand drug release strategy achieved the best anti-inflammatory and antioxidant effects, and they are expected to be a promising carrier in the UC treatment.
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International Journal of Nanomedicine
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2023
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IF 8
Chen Xu,Rijin Song,Pei Lu,Jianchun Chen,Yongqiang Zhou,Gang Shen,Minjun Jiang,Wei Zhang
Introduction Poor cell uptake and incomplete intracellular drug release are the two major challenges for polymeric prodrug-based drug delivery systems (PPDDSs) in cancer treatment.Methods Herein, a PPDDS with pH-induced surface charge-reversal and reactive oxygen species (ROS) amplification for ROS-triggered self-accelerating drug release was developed, which was formed by encapsulating a ROS generation agent (vitamin K3 (VK3)) in pH/ROS dual-sensitive polymetric prodrug (PEG-b-P(LL-g-TK-PTX)-(LL-g-DMA)) based micelle nanoparticles (denoted as PVD-NPs).Results The surface charge of the PVD-NPs can change from negative to positive for enhanced cell uptake in response to tumor extracellular acidity pH. After internalization by cancer cells, PVD-NPs demonstrate dual drug release in response to intracellular ROS-rich conditions. In addition, the released VK3 can produce ROS under the catalysis by NAD(P)H:quinone oxidoreductase-1, which facilitates tumor-specific ROS amplification and drug release selectively in cancer cells to enhance chemotherapy.Conclusion Both in vitro and in vivo experiments demonstrated that the PVD-NPs showed significant antitumor activity in human prostate cancer.
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FOOD AND CHEMICAL TOXICOLOGY
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2022
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IF 5.572
Xinyue Sun,Wenyue Zhang,Yuqi Wang,Yilei Zhang,Xiaojing Liu,Xu Shi,Shiwen Xu
Di(2-ethylhexyl) phthalate (DEHP) and polystyrene microplastics (PS-MPs) are new environmental pollutants that attracted increased attention. At present, the effects and underlying mechanisms of action of combined exposure of DEHP and PS-MPs on the kidney have not been elucidated. To investigate the renal toxicity of DEHP and PS-MPs exposure, we established single and combined DEHP and PS-MPs exposure models in mice and HEK293 cells, respectively. Hematoxylin and eosin staining, transmission electron microscopy , monodansylcadaverine staining, immunofluorescence, real-time quantitative PCR, Western blot analysis and other methods were used to detect relevant indicators. The results showed that the expression levels of ROS/AMPK/ULK1 and Ppargc1α/Mfn2 signaling pathway-related genes were significantly increased in the DEHP and PS-MPs exposure models. The mRNA and protein expression levels of autophagy markers were also upregulated. In addition, we found that the expression levels of mRNAs and proteins in the combined exposure group were more significantly increased than those in the single exposure group. In conclusion, combined exposure to DEHP and PS-MPs caused oxidative stress and activated the AMPK/ULK1 pathway, thereby inducing renal autophagy. Our results enhance the field of nephrotoxicity studies of plasticizers and microplastics and provide new light on combined toxicity studies of DEHP and PS-MPs.
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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
Yang You,Yipu Liu,Chuchu Ma,Jianpei Xu,Laozhi Xie,Shiqiang Tong,Yinzhe Sun,Fenfen Ma,Yukun Huang,Junbin Liu,Wenze Xiao,Chengxiang Dai,Suke Li,Jigang Lei,Qiyong Mei,Xiaoling Gao,Jun Chen
Mesenchymal stem cells (MSCs) exhibited remarkable therapeutic potential in ischemic stroke due to their exceptional immunomodulatory ability and paracrine effect; they have also been regarded as excellent neuroprotectant delivery vehicles with inflammatory tropism. However, the presence of high levels of reactive oxygen species (ROS) and an oxidative stress environment at the lesion site inhibits cell survival and further therapeutic effects. Using bioorthogonal click chemistry, ROS-responsive luteolin-loaded micelles were tethered to the surface of MSCs. As MSCs migrated to the ischemic brain, the micelles would achieve ROS-responsive release of luteolin to protect MSCs from excessive oxidative damage while inhibiting neuroinflammation and scavenging ROS to ameliorate ischemic stroke. This study provided an effective and prospective therapeutic strategy for ischemic stroke and a framework for a stem cell-based therapeutic system to treat inflammatory cerebral diseases.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Wenli Zhang,Maoyuan Sun,Yun Liu,Yu Zhang,Lian Xu,Ying Luo,Qianying Du,Jie Xu,Jia Liu,Jun Zhou,Haitao Ran,Zhigang Wang,Junrui Wang,Dajing Guo
Thrombotic diseases cause significant risks of disability and death worldwide. However, conventional thrombolytic drugs have short half-lives, poor targeting capabilities, limited therapeutic effects， and narrow therapeutic windows. Moreover, most basic studies focus only on thrombolytic efficiency and ignore the inflammatory factors that promote thrombosis progression, such as reactive oxygen species (ROS)-mediated oxidative stress. Therefore, to achieve comprehensive and effective thrombolytic management, both targeted thrombolytic therapy and the elimination of inflammatory factors must be achieved. In this study, we developed a platelet membrane (PM)-functionalized hollow mesoporous Prussian blue nanomedicine (HMPB-rtPA@PM), which was innovatively coassembled from two FDA-approved drugs (Prussian blue (PB) and alteplase (rtPA)) and showed marked advantages in both thrombi targeting and photothermal/pharmacological synergistic fibrinolysis. Moreover, HMPB-rtPA@PM exhibited the potential to inhibit platelet aggregation and regulate the inflammatory microenvironment by scavenging ROS. As expected, this nanomedicine not only achieved more efficient thrombolysis in both thrombus models but also delayed thrombosis progression through therapeutic visualization in the black tail model. Such rational therapeutic principle provides a broad platform for the comprehensive management of thrombotic diseases.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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IF 6.8
Wan-He Li,Zheng-Ting-Yan Xiang,An-Xin Lu,Su-Su Wang,Chong-Huai Yan
Manganese (Mn) is an essential trace element that maintains many normal physiological functions. However, multi-system disorders would occur once overexposure to Mn, especially neurotoxicity. Despite evidence demonstrating the critical role of ROS-activated JNK/FOXO3a signaling pathway in neuronal survival, the specific mechanisms by which it contributes to Mn-induced neurotoxicity are still unclear. The objectives of this study was to examine the modulation of the JNK/FOXO3a signaling pathway, which is activated by ROS, in Mn-induced apoptosis, using a rat brain astrocyte cell line (CTX cells). This study found that a dose-dependent decrease in cell viability of CTX cells was observed with 150, 200, 250, 300 μmol/L Mn. The results of apoptosis-related protein assay showed that Mn decreased the expression of anti-apoptotic protein Bcl-2 and enhanced the expression of apoptosis-related proteins like Bax and Cleaved-Caspase3. In addition, treatment with Mn resulted in elevated ROS levels and increased phosphorylation levels of JNK. Conversely, phosphorylation of nuclear transcription factors FOXO3a, which regulates expression of transcription factors including Bim and PUMA, was decreased. Depletion of ROS by N-acetyl- L -cysteine (NAC) and inhibition of the JNK pathway by SP600125 prevented Mn-induced JNK/FOXO3a pathway activation and, more importantly, the level of apoptosis was also significantly reduced. Confirmation of Mn-induced apoptosis in CTX cells through ROS generation and activation of the JNK/FOXO3a signaling pathway was the outcome of this study. These findings offer fresh insights into the neurotoxic mechanisms of Mn and therapeutic targets following Mn exposure.
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高影响因子
Small
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2023
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IF 13.3
Xiaotong Chen,Lianying Zhang,Haifeng Zeng,Wei Meng,Guijiang Liu,Wenhua Zhang,Pei Zhao,Qun Zhang,Ming Chen,Jinxiang Chen
Rheumatoid arthritis (RA) is a chronic autoimmune disease commonly associated with the accumulation of hyperactive immune cells (HICs), particularly macrophages of pro-inflammatory (M1) phenotype, accompanied by the elevated level of reactive oxygen species (ROS), decreased pH and O 2 content in joint synovium. In this work, an immunomodulatory nanosystem (IMN) is developed for RA therapy by modulating and restoring the function of HICs in inflamed tissues. Manganese tetraoxide nanoparticles (Mn 3 O 4 ) nanoparticles anchored on UiO-66-NH 2 are designed, and then the hybrid is coated with Mn-EGCG film, further wrapped with HA to obtain the final nanocomposite of UiO-66-NH 2 @Mn 3 O 4 /Mn-EGCG@HA (termed as UMnEH). When UMnEH diffuses to the inflammatory site of RA synovium, the stimulation of microwave (MW) irradiation and low pH trigger the slow dissociation of Mn-EGCG film. Then the endogenously overexpressed hydrogen peroxide (H 2 O 2 ) disintegrates the exposed Mn 3 O 4 NPs to promote ROS scavenging and O 2 generation. Assisted by MW irradiation, the elevated O 2 content in the RA microenvironment down-regulates the expression of hypoxia-inducible factor-1α (HIF-1α). Coupled with the clearance of ROS, it promotes the re-polarization of M1 phenotype macrophages into anti-inflammatory (M2) phenotype macrophages. Therefore, the multifunctional UMnEH nanoplatform, as the IMN, exhibits a promising potential to modulate and restore the function of HICs and has an exciting prospect in the treatment of RA.
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 19
·11578
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IF 6.208
Bin Liu,Ming Tang,Hui Chen
Bark beetles mainly rely on detoxification enzymes to resist the host tree’s defense against oleoresin terpenes. Cytochrome P450 enzymes (CYPs) play an important role in the detoxification of plant allelochemicals and pesticides in insect. One P450 gene (DaCYP4BQ1) is associated with the response of (+)-α-pinene inDendroctonus armandi. However, the regulatory mechanism of this P450 gene response to (+)-α-pinene is still unknown. In this study, spatiotemporal expression profiling indicated thatCYP4BQ1was highly expressed in adult and larval stages ofD. armandi, and it was predominantly expressed in fat body, midgut, and Malpighian tubules of adults. Moreover, the expression ofCYP4BQ1significantly increased after exposure to (+)-α-pinene, and depletion of it decreased the tolerance of adults to (+)-α-pinene. In addition, (+)-α-pinene treatment induced the expression of the transcription factors cap ‘n’ collar isoform C (CncC) and its binding factor muscle aponeurosis fibromatosis (Maf), elevated the level of hydrogen peroxide (H2O2), and increased the activities of antioxidant enzymes. SilencingCncCsuppressedCYP4BQ1expression and enhanced the susceptibility of beetles to (+)-α-pinene. Similarly, application of the reactive oxygen species (ROS) scavenger N-acetylcysteine reduced the production and accumulation of H2O2, suppressed the expression ofCncC, Maf, andCYP4BQ1and led to decreased tolerance of adults to (+)-α-pinene. In contrast, ingestion of the CncC agonist curcumin elevatedCYP4BQ1expression and enhanced (+)-α-pinene tolerance. The results demonstrate that, inD. armandi, (+)-α-pinene inducesCYP4BQ1via activation of the ROS/CncC signaling pathway.Keywords:Dendroctonus armandi;phytochemical tolerance;cytochrome P450;oxidative burst;CncC pathway
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ACS Nano
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2022
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IF 18.027
Ruizhi Hu,Chen Dai,Caihong Dong,Li Ding,Hui Huang,Yu Chen,Bo Zhang
Atherosclerosis, driven by chronic inflammation in the artery walls, underlies several severe cardiovascular diseases. However, currently available anti-inflammatory-based strategies for atherosclerosis treatment suffer from compromised therapeutic efficacy and undesirable therapeutic outcome. Herein, a distinct tetrapod needle-like PdH nanozyme was designed and engineered for efficient atherosclerosis treatment by the combinatorial reactive oxygen species (ROS) scavenging, hydrogen anti-inflammation, and autophagy activation. After loading into macrophages and targeted delivery to arterial plaques, these multifunctional nanozymes efficiently decreased the ROS levels and significantly suppressed the inflammation-related pathological process, exerting the distinct antioxidation and anti-inflammatory performance for alleviating atherosclerosis development. Especially and importantly, the specific spiky morphology of the PdH nanoenzyme further triggered a strong autophagy response in macrophages, synergistically maintaining the cellular homeostasis and alleviating atherosclerosis development. Both in vitro and in vivo results confirmed the synergy among the antioxidation, anti-inflammatory, and autophagy activation, suggesting that the combinatorial engineering of nanomedicines with intrinsic multiple therapeutic functions and topology-induced biological effects is highly preferable and effective for achieving the high therapeutic performance and desirable therapeutic outcome on atherosclerosis management and therapy.
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JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2022
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IF 6.117
Lingli Zhao,Mengfei Zheng,Hao Cai,Juan Chen,Yan Lin,Fangbin Wang,Lu Wang,Xian Zhang,Jian Liu
Mitochondrial reactive oxygen species (ROS)generation plays an essential role in the process of adipocyte differentiation and is involved in the development of obesity and associated metabolic diseases . Various dietary flavonoids possess the substantial anti-adipogenic activity. However, it is unclear whether these flavonoids inhibit adipocyte differentiation by reducing ROS generation. In this study, the effects of six common dietary flavonoids on adipocyte differentiation were assessed in 3T3-L1 cells. The flavonoids with the same backbone of 5,7-dihydroxylflavone, including flavones apigenin , chrysin , luteolin and flavonols kaempferol , myricetin , quercetin , dose-dependently inhibited 3T3-L1 adipocyte differentiation, suggesting an associated hierarchy of inhibitory capability: luteolin > quercetin > myricetin > apigenin/kaempferol > chrysin. Meanwhile, six flavonoids were found to inhibit adipogenic gene expression and the early stage of adipocyte differentiation. Among the tested flavonoids, luteolin significantly reduced both intracellular and mitochondrial ROS generation during adipocyte differentiation. Further, luteolin treatment depressed the elevation of H 2 O 2 concentration in the early stage of 3T3-L1 differentiation and reversed the facilitated effects of exogenous H 2 O 2 on 3T3-L1 adipocyte differentiation and ROS generation. Altogether, the activity comparison of six dietary flavonoids identifies that luteolin inhibits 3T3-L1 adipocyte differentiation through reducing ROS generation, elucidating a new mechanism underlying the anti-adipogenic actions of flavonoids.
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BIOMACROMOLECULES
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2022
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IF 6.978
Yuan Wei,Jingze Liu,Gongyan Liu,Shuai Gao,Dimeng Wu,Li Yang,Rifang Luo,Fanjun Zhang,Yunbing Wang
In traditional blood-contacting medical devices, infection and thrombosis are easily formed on the surface of the materials. In addition, inflammation is also a clinical complication that cannot be ignored. More importantly, there is a mutually promoting relationship between the inflammatory response and the infection as well as thrombosis. In this work, we propose a self-adaptive anti-inflammatory coating strategy combined with anti-infection and anticoagulant capacity, which was accomplished based on nano-Ag particles and dexamethasone (Dex)-loaded hydrogel coating. The coating loaded with nano-Ag endows it with good bactericidal performance, including Gram-positive and Gram-negative bacteria. As an anti-inflammatory drug, Dex was grafted onto hydrogel coating by a reactive oxygen species (ROS)-cleavable thioketal (TK) bond and released upon the trigger of an inflammatory environment, blocking further inflammatory cascade, providing self-adaptive anti-inflammatory properties, and avoiding side effects of the drug. It was demonstrated that the coating worked as a precise strategy to resist coagulation, infection, and inflammation, provided a new perspective for designing clinical complication-conformable coatings, and had great application prospects on blood-contacting medical devices.
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