ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Yahong Liu,Longfei Miao,Yuying Guo,Renbin Yuan,Xuejiao Li,Xinxin Wang,Xiaona Lin,Hongqi Tian
Protecting the body from radiation damage is a huge medical challenge. Amifostine and curcumin are both effective radioprotectants, but their use has been greatly restricted due to various reasons including low bioavailability. Nanoscale drug delivery systems of poly(ethylene glycol)–poly(ε-caprolactone) copolymers can improve the bioavailability of drugs due to excellent biocompatibility, biodegradability, and long circulation characteristics. In this study, a new reactive oxygen species-sensitive nanocarrier fabricated by linking curcumin and thioketal to poly(ethylene glycol)–poly(ε-caprolactone) polymer was used for delivery of WR-1065 (the active ingredient of amifostine). The content of curcumin in this polymer was about 7.6%, and the drug loading of WR-1065 was 44%. The WR-1065-loaded nanoparticles (NPs) had an average size of 128.6 nm and uniform spherical morphology. These WR-1065-loaded NPs reduced the metabolism of curcumin and WR-1065 in the gastrointestinal tract and could be well absorbed by cells and distributed to multiple organs. Compared with a single drug, oral administration of WR-1065-loaded NPs demonstrated obvious radioprotective effects on the hematopoietic system and prevented intestinal injury. The 30-day survival rate after half-lethal dose (7.2 Gy) of total body irradiation was 100%. In general, WR-1065-loaded NPs improved the oral bioavailability of WR-1065 and curcumin. This multifunctional nanocarrier provides a possibility for combination therapy in treating ionizing radiation damage.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Ye Qin,Zhou Li,Jin Ping,Li Lei,Zheng Shuwen,Huang Zhao,Liu Jiayang,Qin Siyuan,Liu Hao,Zou Bingwen,Xie Ke
Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide, yet effective treatment remains a clinical challenge. Guaiazulene (GYZ), a cosmetic color additive, has previously been characterized as a potential antitumor agent due to observed anticancer effects. However, the efficacy of GYZ in the treatment of NSCLC and the involved molecular mechanisms remain largely unknown. Here, we indicated a role for GYZ in the suppression of NSCLC both in vitro and in vivo via triggering reactive oxygen species (ROS)-induced apoptosis. Concomitantly, GYZ induced complete autophagic flux in NSCLC cells via inhibiting the Akt/mTOR signaling pathway, which displayed cytoprotective effect against GYZ-induced growth suppression. Accompanied with autophagy inhibition obviously enhanced the effects of GYZ. Notably, GYZ acts synergistically with paclitaxel in the suppression of NSCLC in vitro. Together, our results for the first time reported that GYZ suppressed the proliferation of NSCLC and suggested a potential strategy for inhibiting NSCLC growth by combinational use of GYZ and autophagy inhibitors.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2021
·
IF 9.811
Ke Li,Jian Yang,Jinlou Gu
The creation of artificial microenvironments with specific functionalities to mimic multiple cascade biocatalytic processes in cells is highly desirable. Here, Zr-based large-pore mesoporous metal–organic frameworks (mesoMOFs) were successfully developed for the construction of such spatially organized cascade bioreactors. Thanks to the mediating effect of the Hofmeister ion and the flexibility of Zr-MOFs, large mesopores and functional microporous mesopore walls were integrated into a single nanoplatform, ensuring the efficient mass exchange between the interconnected pore units with different sizes. As a proof of concept, natural superoxide dismutase and catalase mimic were spatially positioned in these hierarchical mesoMOFs, which formed a cascade antioxidant defense system and presented an efficient intracellular reactive oxygen species scavenging ability. This model is expected to set a conceptual guideline for the design of compartmentalized bioreactors in nanoscale MOFs to mediate the complex intracellular catalytic networks.
✓ 已验证
产品关联
DOI
高影响因子
Natural Product Communications
·
2021
·
IF 0.986
Wenyu Xin,Ming Jing,Junjie Yang,Meiling Wang,Guige Hou,Qiaoyun Wang,Leiming Zhang,Chunhua Wang
Emerging evidence indicates that NOD-like receptor protein 3 (NLRP3) inflammasome-induced inflammation plays a critical role in the pathogenesis of Parkinson’s disease (PD). Baicalein has been considered as a possible option for PD treatment based on its anti-neuroinflammatory effects. However, no studies have elucidated the precise mechanisms underlying the anti-neuroinflammatory activity of baicalein, particularly inflammasome-mediated effects. In this present study, rotenone-induced PD mice and BV2 microglia were used to investigate the anti-neuroinflammatory effects of baicalein and explore its underlying mechanism in vivo and in vitro. The results demonstrated that baicalein alleviated motor impairments and attenuated several inflammatory responses in rotenone-induced PD mice. Also, baicalein inhibited the expression of NLRP3 and activated caspase-1 in brain tissues. Correspondingly, baicalein prominently suppressed the inflammatory response in BV2 microglia induced by rotenone. Furthermore, in vitro data showed that baicalein suppressed the expression of NLRP3 and activated caspase-1 by abrogating the upregulation of ROS, as well as by inhibiting the TLR4/NF-κB signaling cascade. Overall, the results of the present study indicated that baicalein exerted anti-neuroinflammatory effects partly by inhibiting activation of the NLRP3 inflammasome, and targeting NLRP3 inflammasome signaling offers a novel therapeutic strategy for PD treatment.
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
·
IF 4.932
Yifan Wang,Wen Zhu,Dandan Lu,Chuzhao Zhang,Yue Wang
Activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome plays a crucial role in the inflammatory responses of monosodium urate (MSU) crystal-induced gouty arthritis. Therefore, the molecular basis of NLRP3 inflammasome is very valuable in developing potential therapeutic drugs for gout. Tetrahydropalmatine (THP), the main active component of the traditional Chinese medicinal herb Corydalis yanhusuo, has shown prominent anti-inflammatory and analgesic activities, but to date, these effects have not been investigated exhaustively on gout. This study indicated that THP attenuated pain and swelling in an MSU-induced acute gout model by decreasing pro-inflammatory cytokine production and inflammatory cell infiltration. THP exerted its actions by suppressing NLRP3 inflammasome activation and subsequent formation of caspase-1. Furthermore, results showed that THP alleviated MSU-induced reactive oxygen species (ROS) generation, upstream of NLRP3 inflammasome activation, by an increase in the activities of antioxidant enzymes both in vitro and in vivo. In conclusion, our study suggests that THP suppressed ROS-mediated NLRP3 inflammasome activation in MSU-induced inflammatory responses, which highlights its therapeutic potential in gouty arthritis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2021
·
IF 5.194
Yilong Cui,Miao Song,Bonan Xiao,Menglin Liu,Pengli Liu,Yanfei Han,Bing Shao,Yanfei Li
The problem of excessive aluminum (Al) content in food is widespread. After Al enters the body, it can cause mineral metabolism imbalance and reactive oxygen species (ROS) overproduction, which ultimately leads to bone impairment. ROS is mainly produced in mitochondria and acts on mitochondria. Mitochondrial damage is closely related to mitophagy and apoptosis . In order to clarify whether ROS-mediated mitophagy and apoptosis are involved in Al-induced femoral impairment, forty-eight male C57BL/6 N mice were exposed to AlCl 3 (179.3 mg/kg) and/or NAC (100 mg/kg) for 90 days. Our results showed that NAC inhibited the mitophagy and apoptosis, and alleviated growth inhibition, mineral metabolism imbalance, structural damage, decreased bone mineral density and decreased bone formation factor expressions in the femora of Al-treated mice. These results suggest that ROS-mediated mitophagy and apoptosis are involved in Al-induced femoral impairment in mice, exogenous ROS clearance is a potential strategy for the treatment of Al-induced bone impairment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2019
·Vol. 16
·期 27
·1902123
·
IF 10.856
Shichao Lin,Yuan Cheng,He Zhang,Xiaoyu Wang,Yuye Zhang,Yuanjian Zhang,Leiying Miao,Xiaozhi Zhao,Hui Wei
The global tobacco epidemic is still a devastating threat to public health. Toxic reactive oxygen species (ROS) in the cigarette smoke cannot be efficiently eliminated by currently available cigarette filters. The resultant oxidative stress causes severe lung injury and further diseases. To tackle this challenge, herein, a novel copper tannic acid coordination (CuTA) nanozyme is reported as a highly active and thermostable ROS scavenger. The CuTA nanozyme exhibits intrinsic superoxide dismutase-like activity, catalase-like activity, and hydroxyl radical elimination capacity. These synergistic antioxidant abilities make the CuTA nanozyme a promising candidate for the improvement of commercial cigarette filters. Mouse model results show that commercial cigarettes loaded with CuTA nanozyme efficiently scavenge ROS in the cigarette smoke, reduce oxidative stress–induced lung inflammation, and minimize the resultant acute lung injury. The developed CuTA nanozyme offers an efficient ROS scavenger with multiple antioxidant ability and opens up new opportunities for the modification of cigarette filters to reduce the toxic effects of cigarette smoke.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2019
·
IF 5.108
Yiran Liang,Bizhang Dong,Nannan Pang,Jiye Hu
The widespread use of abamectin has recently raised safety concerns as abamectin has yielded various toxicities to non-target organisms. However, the underlying mechanisms of abamectin-induced toxicity are still largely unknown. The present study aimed to investigate the abamectin-induced cytotoxicity in mouse macrophage cells (RAW264.7) and its underlying mechanisms. Abamectin treatment caused oxidative stress as characterized by increased intensity of the ROS indicator. Abamectin also led to DNA damage as demonstrated by increased 8-OHdG/dG ratio in cells even at a relatively low dose (NOAEL). Pretreatment with catalase-PEG, a ROS inhibitor, attenuated abamectin-induced DNA damage, indicating that ROS overproduction should be the reason for abamectin-induced DNA damage. The effects of abamectin on ROS elimination and generation were also investigated, and the results showed that abamectin induced concentration-dependent alteration in the expression and activities of CAT, SOD, GPx enzymes and GSH level (ROS elimination), but had limited effects on the expression and activities of NOX , mitochondrial complex I and III (ROS production) in RAW264.7 cells. Therefore, the effects of abamectin on ROS elimination should be the main reason for abamectin-induced oxidative stress in RAW264.7 cells. Abamectin treatment activated MAPK and ATM/ATR signaling pathways as demonstrated by increased phosphorylation of JNK, ATM and ATR. In addition, inhibiting JNK and ATM/ATR signaling pathways partially rescued the decrease in cell viability, indicating that abamectin-induced ROS overproduction and DNA damage might finally lead to cytotoxicity through JNK and ATM/ATR signaling pathways. These findings should be useful for the more comprehensive assessment of the toxic effects of abamectin.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2019
·
IF 6.638
Bingjun Sun,Yao Chen,Han Yu,Chen Wang,Xuanbo Zhang,Hanqing Zhao,Qin Chen,Zhonggui He,Cong Luo,Jin Sun
The combination of chemotherapy with photodynamic therapy (PDT) holds promising applications in cancer therapy. However, co-encapsulation of chemotherapeutic agents and photosensitizers (PS) into the conventional nanocarriers suffers from inefficient co-loading and aggregation-caused quenching (ACQ) effect of PS trapped in dense carrier materials. Herein, we report a light-activatable photodynamic PEG-coated prodrug nanoplatform for core–shell synergistic chemo-photodynamic therapy. A novel photodynamic polymer is rationally designed and synthesized by conjugating pyropheophorbide a (PPa) to polyethylene glycol 2000 (PEG 2k ). PPa is used as the hydrophobic and photodynamic moiety of the amphipathic PPa-PEG 2k polymer. Then, a core–shell nanoassembly is prepared, with an inner core of a reactive oxygen species (ROS)-responsive oleate prodrug of paclitaxel (PTX) and an outer layer of PPa-PEG 2k . PPa-PEG 2k serves for both PEGylation and PDT. Instead of being trapped in the inner core, PPa in the outer PPa-PEG 2k layer significantly alleviates the ACQ effect. Under laser irradiation, ROS generated by PPa-PEG 2k not only is used for PDT but also synergistically promotes PTX release in combination with the endogenous ROS overproduced in tumor cells. The photodynamic PEG-coated nanoassemblies demonstrated synergistic antitumor activity in vivo . Such a unique nanoplatform, with an inner chemotherapeutic core and an outer photodynamic PEG shell, provides a new strategy for synergistic chemo-photodynamic therapy. Statement of Signification The combination of chemotherapy with photodynamic therapy (PDT) holds promising prospects in cancer therapy. However, it remains a tremendous challenge to effectively co-deliver chemotherapeutic drugs and photosensitizers into tumors. Herein, we construct a photodynamic PEGylation-coated prodrug-nanoplatform for high-efficiency synergistic cancer therapy, which is composed of a light-activatable PPa-PEG 2k shell and a ROS-responsive paclitaxel (PTX) prodrug core. The PPa-PEG 2k -generated ROS not only was used for synergistic PTX release but also synergistically facilitated tumor cell apoptosis in combination with PTX-initiated chemo-cytotoxicity. The light-activatable nanoassemblies exhibited multiple drug delivery advantages including high co-loading efficiency, self-enhanced PTX release, extended circulation time, favorable biodistribution , and potent synergistic anticancer activity. Our findings provide a new strategy for the rational design of advanced nano-DDS for high-efficiency combinational chemo-photodynamic therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2017
·Vol. 12
·期 3
·e0173712
·
IF 2.806
Xianzhi Qu,Jiyao Sheng,Luyan Shen,Jing Su,Yunjie Xu,Qi Xie,Yao Wu,Xuewen Zhang,Liankun Sun
The tumor cells have some metabolic characteristics of the original tissues, and the metabolism of the tumor cells is closely related to autophagy. However, the mechanism of autophagy and metabolism in chemotherapeutic drug resistance is still poorly understood. In this study, we investigated the role and mechanism of autophagy and glucose metabolism in chemotherapeutic drug resistance by using cholangiocarcinoma QBC939 cells with primary cisplatin resistance and hepatocellular carcinoma HepG2 cells. We found that QBC939 cells with cisplatin resistance had a higher capacity for glucose uptake, consumption, and lactic acid generation, and higher activity of the pentose phosphate pathway compared with HepG2 cells, and the activity of PPP was further increased after cisplatin treatment in QBC939 cells. It is suggested that there are some differences in the metabolism of glucose in hepatocellular carcinoma and cholangiocarcinoma cells, and the activation of PPP pathway may be related to the drug resistance. Through the detection of autophagy substrates p62 and LC3, found that QBC939 cells have a higher flow of autophagy, autophagy inhibitor chloroquine can significantly increase the sensitivity of cisplatin in cholangiocarcinoma cells compared with hepatocellular carcinoma HepG2 cells. The mechanism may be related to the inhibition of QBC939 cells with higher activity of the PPP, the key enzyme G6PDH, which reduces the antioxidant capacity of cells and increases intracellular ROS, especially mitochondrial ROS. Therefore, we hypothesized that autophagy and the oxidative stress resistance mediated by glucose metabolism may be one of the causes of cisplatin resistance in cholangiocarcinoma cells. It is suggested that according to the metabolism characteristics of tumor cells, inhibition of autophagy lysosome pathway with chloroquine may be a new route for therapeutic agents against cholangiocarcinoma.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
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.
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）