CHEMICAL ENGINEERING JOURNAL
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2021
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IF 13.273
Richun Liu,Bo Zhou,Hong Zhang,Yangwu Chen,Chunmei Fan,Tao Zhang,Tian Qin,Jie Han,Shichen Zhang,Xiao Chen,Weiliang Shen,Jiang Chang,Zi Yin
In the inflammatory environment of tendinopathy, tendon stem/progenitor cells (TSPCs) have been demonstrated to aberrantly differentiate into osteochondral lineage causing late-stage heterotopic ossification (HO) of the tendon, which severely damages tissue function and worsens patients’ activities. However, no effective treatment for tendinopathy currently exist because the mechanism underlying the TSPCs abnormal differentiation is unclear. In this article, high levels of reactive oxygen species (ROS) were found in tendinopathy samples. In vitro results revealed that proanthocyanidins (PC) can potentially regulate the differentiation of TSPCs by scavenging excess ROS, which would promote tenogenesis instead of chondrogenesis or osteogenesis. Moreover, in vivo results demonstrated that PC-loaded mesoporous silica nanocomposite (MSNs-PC) hinders the recurrence of HO in repaired tendons owing to the inhibition of oxidative stress, showing anti-inflammatory effects. Our findings indicate a high level of ROS in tendinopathy, which is probably the cause of aberrant differentiation of TSPCs. MSNs-PCs can effectively ameliorate HO of the tendon by scavenging excess ROS, providing a promising avenue to for other ROS-related diseases.
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ENVIRONMENTAL TOXICOLOGY
·
2021
·Vol. 36
·期 8
·1674-1682
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IF 4.119
Jun Shi,Xueting Wang,Lulu Chen,Huiping Deng,Min Zhang
Brominated flame retardants (BFRs), such as, 1,2,5,6-tetrabromocyclooctane (HBCD), 1,2-dibromo-4-(1,2-dibromopropyl)cyclohexane (TBECH), and 1 1,2-bis-(2,4,6-tribromophenoxy)ethane (BTBPE), have garnered increasing attention due to their potent biological effects. In the present study, the toxicity of HBCD, TBECH, and BTBPE in human vascular endothelial cells (ECs) was explored. The data showed that HBCD, TBECH, and BTBPE induced cytotoxicity, namely dose–dependent cell viability reduction, cell membrane permeability and apoptosis increase, migration, and lumen formation inhibition. Moreover, HBCD was found to be more toxic than BTBPE or TBECH. Exposure to HBCD, TBECH, and BTBPE led to the production of reactive oxygen species, mitochondrial superoxide generation, and mitochondrial membrane potential collapse, implying that reactive stress caused the cytotoxicity. The ATP content, glutathione content, superoxide dismutase, and MDA activities were reduced, indicating that mitochondrial dysfunction may be the key mechanisms responsible for apoptosis. The present study suggested that mitochondria are a new target of BFRs in ECs and further deepened our understanding of the developmental toxicity of BFRs.
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ACS Applied Bio Materials
·
2021
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IF 0
Ning Zhang,Daquan Wang,Xunan Jing,Tingting Yang,Hongbo Yang,Lingjie Meng
In the past decades, polymer–drug conjugates of anticancer agents have gained much attention due to their enhanced aqueous solubility, improved pharmacokinetics, and better drug utilization than their conventional insoluble counterparts. Several polymer–drug conjugates have entered the third phase of clinical trials yet suffer from inherent deficiencies, including uncontrolled drug release and unclear degradation mechanisms. In this study, a pH/reactive oxygen species (ROS) dual-responsive PEG-doxorubicin (DOX) conjugate (denoted as TPD) was synthesized through acyl alkynyl-amine click reaction by PEG dipropiolate (PEGB), amine-terminated thioketal (TKL), and doxorubicin (DOX). Due to the generated ene-amine and thioketal in the backbone, the prepared amphiphilic TPD not only has a high drug loading ratio for photosensitizer chlorin e6 (Ce6) but also has the sensitivity to the acidic tumor microenvironment (TME) and ROS. Considering the complex conditions of TME, the prepared TPD@Ce6 nanoparticles (NPs) might respond to the relatively low pH and release Ce6 initially, and upon laser radiation, Ce6 produces abundant singlet oxygen (1O2) to achieve a programmable accelerated release of DOX and more Ce6 at the tumor site. In addition, the NIR fluorescence of DOX could monitor drug delivery and controlled release. The developed TPD@Ce6 NPs can realize the targeted tumor in combination therapy with negligible cytotoxicity on normal tissues.
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Biomaterials Science
·
2020
·Vol. 8
·期 21
·5931-5940
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IF 6.183
Xiang Zhan,Xuan Nie,Fan Gao,Cong Zhang,Ye-Zi You,Yue Yu
Nanomedicine has attracted growing attention due to its designability and functionality, as well as its excellent pharmacokinetics with limited side effects, and recently, combined therapies have become desirable as they can obtain enhanced therapeutic efficacy by using nanomedicine. Herein, we have reported a functional drug delivery system with a dual response to temperature and reactive oxygen species to efficiently eliminate pancreatic cancer cells in a combined therapy strategy. Functional micelles with camptothecin (CPT) in the core and indocyanine green (ICG) on the surface could effectively accumulate in tumor sites through the EPR effect. The ROS in the tumor microenvironment trigger the conversion of an amino-based copolymer to a carboxy based copolymer, releasing the loaded ICG to reduce the size of the micelles with high penetration in tumor tissue. On the one hand, under 808 nm light irradiation, the micelles will produce the heat to kill tumor cells via photothermal therapy. On the other hand, the generated heat could further trigger the transition of a copolymer from a hydrophobic to a hydrophilic state, releasing the loaded CPT into the deep tumor cells to achieve chemotherapy. The in vitro and in vivo experiments revealed that this combined therapy could combat pancreatic cancer cells with an enhanced therapeutic effect.
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高影响因子
Food & Function
·
2020
·Vol. 11
·期 6
·5156-5165
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IF 4.171
Yu-Sheng Shi,Xiao-Xing Li,Hao-Tian Li,Yan Zhang
Liver fibrosis is a histological change that often occurs due to hepatic stellate cell (HSC) activation and excessive formation of an extracellular matrix in the liver. Pelargonidin (PEL) is a natural anthocyanidin existing in blueberries, berries, strawberries, and red radishes and has been demonstrated to possess health beneficial effects. Herein, we investigated the effect of PEL on liver fibrosis induced by CCl4 and hepatic stellate cells induced by transforming growth factor-β (TGF-β). We found that PEL administration prevented liver injury and liver fibrosis induced by CCl4 in a dose-dependent manner. Further data revealed that PEL increased liver nuclear factor E2-related factor 2 (Nrf2) and reduced liver oxidative stress and the expression levels of NLRP3, caspase-1 and IL-1β. In TGF-β-challenged HSCs (LX-2 cells), PEL effectively inhibited the LX-2 cell activation. In addition, the anti-fibrosis effects of PEL in LX-2 cells were abolished by Nrf2 knockdown. In summary, our study demonstrated that PEL ameliorated CCl4-induced liver fibrosis and HSC activation induced by TGF-β. The possible molecular mechanisms of PEL in liver fibrosis may be attributed to its suppression of ROS-NLRP3-IL-1β signaling by Nrf2 activation.
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ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Jun Li,Yun-Jie Wei,Xian-Ling Yang,Wan-Xia Wu,Meng-Qian Zhang,Meng-Yang Li,Zu-E Hu,Yan-Hong Liu,Na Wang,Xiao-Qi Yu
To maximize the utilization and response to the high oxidative stress environment of tumor sites while avoiding the dilemma of enhancing reactive oxygen species (ROS) response in a single way, mitochondrial targeting combined with fluorescent self-reporting polymeric nanocarriers (1K-TPP and 2K-TPP) with grafted structures were synthesized via a chemoenzymatic method in a high yield to simultaneously enhance the drug delivery of endogenous ROS responses. 1K-TPP and 2K-TPP loaded doxorubicin (DOX) at a high content over 12% and formed homogeneous spherical micelles. In vitro, both of them showed promising high sensitivity (detection limit below 200 nM H2O2), fast response, and ratiometric fluorescent self-reporting properties (fluorescent enhancement more than 200 times) to ROS and excellent stability under physiological conditions, while achieving a rapid release of the DOX in response to 1 mM H2O2. Cell co-localization experiments exhibited that they had favorable mitochondrial targeting, and mitochondrial isolation experiments also confirmed that the TPP-modified 1K-TPP selectively accumulated nearly three times in mitochondria than that in total cells. The internalization of 1K-TPP and 2K-TPP into cancer cells was greatly improved by nearly 200% compared to that of unmodified control (1K-OH and 2K-OH) and also explored a unique energy-dependent endocytosis. Furthermore, stimulation of endogenous ROS enhanced the green fluorescence intensity (up to 51.4%) of the linked probe so as to destroy the internal structure of the nanocarriers, achieving self-reporting of the drug’s intracellular release and tracking of the intracellular location of nanocarriers. The cytotoxicity of DOX-loaded 1K-TPP and 2K-TPP in tumor cells with a higher ROS content showed statistical superiority to that of 1K-OH and 2K-OH, benefiting from the extremely good endogenous ROS response sensitivity leading to the differential selective release of drugs. These results demonstrate the potential of 1K-TPP and 2K-TPP, especially for 1K-TPP, as mitochondria-targeted, fluorescent self-reporting nanocarriers for combined enhancement of endogenous ROS responsiveness.
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BIOMATERIALS
·
2019
·
IF 10.273
Yuejun Yao,Jie Ding,Zhaoyi Wang,Haolan Zhang,Jieqi Xie,Yingchao Wang,Liangjie Hong,Zhengwei Mao,Jianqing Gao,Changyou Gao
Reactive oxygen species (ROS) play an important role in the pathogenesis of numerous diseases including atherosclerosis, diabetes, inflammation and myocardial infarction (MI). In this study, a ROS-responsive biodegradable elastomeric polyurethane containing thioketal (PUTK) linkages was synthesized from polycaprolactone diol (PCL-diol ), 1,6-hexamethylene diisocyanate (HDI), and ROS-cleavable chain extender . The PUTK was electrospun into fibrous patches with the option to load glucocorticoid methylprednisolone (MP), which were then used to treat MI of rats in vivo . The fibrous patches exhibited suitable mechanical properties and high elasticity. The molecular weight of PUTK was decreased significantly after incubation in 1 mM H 2 O 2 solution for 2 weeks due to the degradation of thioketal bonds on the polymer backbone . Both the PUTK and PUTK/MP fibrous patches showed good antioxidant property in an oxidative environment in vitro . Implantation of the ROS-responsive polyurethane patches in MI of rats in vivo could better protect cardiomyocytes from death in the earlier stage (24 h) than the non ROS-responsive ones. Implantation of the PUTK/MP fibrous patches for 28 days could effectively improve the reconstruction of cardiac functions including increased ejection fraction , decreased infarction size, and enhanced revascularization of the infarct myocardium.
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MOLECULAR PHARMACEUTICS
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2019
·
IF 4.396
Mengting Lin,Wangwei Guo,Zhentao Zhang,Yi Zhou,Jiejian Chen,Tiantian Wang,Xincheng Zhong,Yiying Lu,Qiyao Yang,Qichun Wei,Min Han,Donghang Xu,Jianqing Gao
Nitrogen mustard (NM) is among the earliest drugs used to treat malignant tumors and it kills tumor cells by cross-linking DNA. Unfortunately, because of the short half-life and unfavorable selectivity, NM causes significant damage to normal tissues. As NM can increase the levels of reactive oxygen species (ROS) in tumor cells, a ROS-activated nitrogen mustard prodrug (NM-Pro) was synthesized and mixed with NM at a specific ratio to obtain an “NM-ROS-NM-Pro-NM” positive feedback system, which ultimately achieves a specific lethal effect on hematological neoplasms. The further encapsulation of NM/NM-Pro in liposomes allows the sustained release of the drug and prolongs the residence time in vivo. Here, we prepared stable liposomes with a uniform particle size of 170.6 ± 2.2 nm. The optimal ratio of NM to NM-Pro in this study was 2:1. The active drug NM in the NM/NM-Pro system continuously stimulated ROS production by the cells, which in turn further activated the NM-Pro to continuously generate NM. The positive feedback pathway between the NM and NM-Pro resulted in the specific death of tumor cells. Furthermore, the K562 hematological neoplasm model was utilized to evaluate the therapeutic effect of NM/NM-Pro liposomes in vivo. After encapsulation in liposomes, the targeting of tumor cells was increased approximately two times compared with that of normal cells, and NM/NM-Pro liposomes exhibited reduced toxicity, without an increase in drug activity compared to the NM/NM-Pro combination. The NM/NM-Pro delivery system exerts a positive feedback effect on ROS production in tumor cells and displays good potential for the specific killing of hematoma cells.
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JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2022
·
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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ACS Nano
·
2022
·
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 Functional Biomaterials
·
2026
·Vol. 17
·期 9
·473
·
IF 5.9
Jiacheng Yu,Chengming Wang,Xiue Ren,Huixia Wang,Yiqiang Huang,Changren Zhou
Elevated levels of reactive oxygen species (ROS) and persistent inflammatory responses represent principal impediments to efficacious wound healing, particularly in mechanically dynamic or infected wound environments. Consequently, multifunctional hydrogel-based dressings capable of integrating coordinated antioxidant, anti-inflammatory, and antimicrobial activities with robust wet-tissue adhesion are highly sought after, yet their development remains limited. Herein, we introduce a curcumin-functionalized polyurethane composite dressing (designated CPFSD), engineered through the incorporation of dopamine-grafted sodium alginate (SD) and ferrocene (Fc), which collectively confer synergistic ROS modulation alongside durable tissue adhesion. Mechanistically, curcumin provides intrinsic antioxidant and anti-inflammatory properties, while Fc facilitates reversible Fe2+/Fe3+redox cycling, thereby augmenting ROS scavenging capacity; concurrently, catechol and hydroquinone moieties present on SD establish stable interfacial interactions with moist biological tissues. Comprehensive physicochemical characterization revealed that CPFSD effectively scavenged over 80% of both DPPH and hydroxyl (·OH) radicals, exhibited greater than 80% antibacterial efficacy against Escherichia coli and Staphylococcus aureus, and demonstrated markedly enhanced adhesive performance while preserving mechanical flexibility and cytocompatibility. In vitro assays further indicated that CPFSD significantly attenuated oxidative stress in L929 fibroblasts and RAW264.7 macrophages, accompanied by downregulation of pro-inflammatory cytokine expression. In a murine full-thickness excisional wound model, CPFSD facilitated accelerated epithelialization, angiogenesis, and wound contraction, achieving wound closure at day 11 without observable systemic toxicity. Collectively, these findings underscore that rational multicomponent design strategies can yield adhesion-capable wound dressings endowed with synergistic therapeutic functionalities suitable for addressing complex pathological wound conditions.
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JOURNAL OF NATURAL PRODUCTS
·
2020
·
IF 3.782
Peng Zhu,Jianqiang Qian,Zhongyuan Xu,Chi Meng,Ji Liu,Wenpei Shan,Weizhong Zhu,Yongjun Wang,Yumin Yang,Wei Zhang,Yanan Zhang,Yong Ling
The natural products piperlongumine and piperine have been shown to inhibit cancer cell proliferation through elevation of reactive oxidative species (ROS) and eventually cell death, but only have modest cytotoxic potencies. A series of 14 novel phenylallylidenecyclohexenone analogues based on piperlongumine and piperine therefore were designed and synthesized, and their pharmacological properties were evaluated. Most of the compounds produced antiproliferative activities against five human cancer cells with IC50 values lower than those of piperlongumine and piperine. Among these, compound 9m exerted the most potent antiproliferative activity against drug-resistant Bel-7402/5-FU human liver cancer 5-FU resistant cells (IC50 = 0.8 μM), which was approximately 10-fold lower than piperlongumine (IC50 = 8.4 μM). Further, 9m showed considerably lower cytotoxicity against LO2 human normal liver epithelial cells compared to Bel-7402/5-FU. Mechanistically, compound 9m inhibited thioredoxin reductase (TrxR) activity, increased ROS levels, reduced mitochondrial transmembrane potential (MTP), and induced autophagy in Bel-7402/5-FU cells via regulation of autophagy-related proteins LC3, p62, and beclin-1. Finally, 9m activated significantly the p38 signaling pathways and suppressed the Akt/mTOR signaling pathways. In conclusion, 9m could be a promising candidate for the treatment of drug-resistant cancer cells and, as such, warrants further investigation.
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