Biomaterials Science
·
2015
·Vol. 4
·期 3
·412-417
·
IF 3.831
Chao Chen,Pan Zheng,Ziyang Cao,Yinchu Ma,Jie Li,Haisheng Qian,Wei Tao,Xianzhu Yang
Redox-responsive polymers exhibit great potential as drug delivery systems. Herein, a redox-responsive PEGylated hyperbranched polyphosphoester (PPE) was synthesized through (A2 + B3) type polycondensation. The obtained hyperbranched PPE can self-assemble into nanoparticles in water. The biocompatibility of the nanoparticles was evaluated. The hydrophobic chemotherapy drug doxorubicin (DOX) can be efficiently encapsulated into the obtained nanoparticles. Such DOX-loaded nanoparticles exhibited excellent stability due to the PEGylation, and showed redox-responsive drug release behavior. In addition, flow cytometric analyses demonstrated that the redox-responsive nanoparticles could be efficiently internalized into the human breast cancer cell line MDA-MB-231, and intracellular glutathione enhanced the intracellular drug release from the redox-responsive hyperbranched PPE based nanoparticles. Therefore, such nanoparticles resulted in the enhanced inhibition of tumor cell growth, suggesting the potential of redox-responsive PEGylated hyperbranched PPE in anticancer drug delivery.
研究领域:
药剂学
·
材料科学
·
肿瘤学
·
聚合物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
·
IF 4.932
Xiaoqi Sun,Xiaotian Wang,Qianqian He,Muqing Zhang,Li Chu,Yang Zhao,Yongchao Wu,Jianping Zhang,Xue Han,Xi Chu,Zhonglin Wu,Shengjiang Guan
Baicalin (BA), a kind of flavonoids compound, comes from Scutellaria baicalensis Georgi (a kind of perennial herb) and has beneficial effects on the cardiovascular system through anti-oxidant, anti-inflammation, and anti-apoptosis actions. However, the therapeutic effects and latent mechanisms of BA on arsenic trioxide (ATO)-induced cardiac toxicity has not been reported. The present research was performed to explore the effects and mechanisms of BA on ATO-induced heart toxicity. Male Kunming mice were treated with ATO (7.5 mg/kg) to induce cardiac toxicity. After the mice received ATO, BA (50 and 100 mg/kg) was administered for estimating its cardioprotective effects. Statistical data demonstrated that BA treatment alleviated electrocardiogram abnormalities and pathological injury caused by ATO. BA could also lead to recovery of CK and LDH activities to normal range and cause a decrease in MDA levels and ROS generation, augmentation of SOD, CAT, and GSH activities. We also found that BA caused a reduction in the expression of proinflammatory cytokines, such as TNF-α and IL-6. Moreover, BA attenuated ATO-induced apoptosis by promoting the expression of Bcl-2 and suppressing the expression of Bax and caspase-3. TUNEL test result demonstrated BA caused impediment of ATO-induced apoptosis. Furthermore, BA treatment suppressed the high expression of TLR4 , NF-κB and P-NF-κB caused by ATO. In conclusion, these results indicate that BA may alleviate ATO-induced cardiac toxicity by restraining oxidative stress, apoptosis, and inflammation, and its mechanism would be associated with the inhibition of the TLR4/NF-κB signaling pathway.
研究领域:
药理学
·
毒理学
·
心脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2023
·
IF 5
Meng Chen,Qilan Hu,Shengquan Wang,Ling Tao,Xiaoxia Hu,Xiangchun Shen
Our previous data confirmed that 1,8-Cineole had an antihypertensive effect in animal models. However, it is unclear whether antihypertension is dependent on the protective effect of 1,8-Cineole on endothelial function and structure. At present, the purpose was to investigate the protective effects of 1,8-Cineole on vascular endothelial tissue in hypertensive rats and human umbilical vein endothelial cells (HUVECs). Our results showed that 1,8-Cineole significantly reduced the blood pressure and improved the vascular endothelial lesion , attenuated vascular oxidative stress and inflammation induced by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) in rats. Pretreatment with 1,8-Cineole was able to inhibit the increase in malondialdehyde (MDA) and reactive oxygen species (ROS) induced by L-NAME, and increased the release and expression of superoxide dismutase (SOD) and nitric oxide (NO). In addition, 1,8-Cineole also reversed the increase of autophagy-associated protein LC3Ⅱ/LC3Ⅰ and the decrease of P62 in vivo and in vitro respectively. There was a synergistic effect between PI3K agonists and drugs, while PI3K inhibitors blocked the efficacy of 1,8-Cineole. The addition of autophagy inhibitor chloroquine increases the expression of eNOS. Taken together, our results indicate that 1,8-Cineole has potential beneficial promising antihypertension depending on the integrity of vascular endothelial structure and function induced by L-NAME, and the mechanism involves ameliorating autophagy by regulating of PI3K/mTOR.
研究领域:
药理学
·
心血管疾病
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2023
·
IF 6.7
Jie Dai,Zhiyi Peng,Shuwei Shen,Binbin Huang,Lili Ren,Jia Liu,Chia Hung Chen,Guoguang Chen
The dysfunction of intracellular proteins is frequently associated with various diseases, such as cancer. The exogenous proteins in cells are usually assembled with specific configurations due to physiological confinement/crowding to exhibit novel features in protein structure, folding or conformational stability, distinguished with their behaviors in buffer solutions. Here, we synthesized exogenous proteins in a confined/crowded condition, to explore protein activity within the cells. The findings suggested that the confinement and crowding effects on protein activity are heterogeneous; they showed an inhibitory consequence on HRP by decreasing Km (from ~9.5- and ~21.7-fold) and Vmax (from ~6.8- and ~20.2-fold) lower than that of dilute solutions. Interestingly, the consequences on Cyt C seem more complicated, and the crowding exerts a positive effect by increasing Km ~3.6-fold and Vmax ~1.5-fold higher than that of dilute solutions; however, the confinement takes a negative consequence by decreasing Km ~2.0 and Vmax ~8.3 times. Additionally, in contrast to traditional nanoparticles-based confinement models, we synthesized a biodegradable nanoparticle to mimic the confined space, and the biggest advantage of this novel model is that the particles can be degraded and thus it can provide more intuitive observations of the target protein properties under the confinement and after release. Furthermore, we also evaluated protein activity in different cellular environments, indicating the exogenous protein activity was closely related to the crowdedness of cellular environments, and the inhibition of protein activity in MDA-MB-231 cancer cells was more obvious than HEK293 normal cells. Finally, SAXS analysis revealed the correlation between the protein conformation and the different environments. Our work will provide a unique way for precisely assessing whether the target cellular environments are native matrix in which specific exogenous protein drugs delivered to function or whether they display a therapeutic role, which is of great significance for screening and development of new drugs.
研究领域:
生物物理学
·
细胞生物学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Hui Zhang,Qingwen Xue,Zihan Zhou,Ningning He,Shangyong Li,Cheng Zhao
Breast cancer (BC) is the most common malignancy in women worldwide, and the standard treatment is chemotherapy or radiotherapy after surgery. In order to reduce the side effects of chemotherapy, various nanoparticles (NPs) have been discovered and synthesized, which has become a promising treatment for BC. In this study, a co-delivery nanodelivery drug system (Co-NDDS) was designed and synthesized with 2,3-dimercaptosuccinic acid (DMSA) coated Fe 3 O 4 NPs as core encapsulated into chitosan/alginate nanoparticles (CANPs) shell, doxorubicin (DOX) and hydroxychloroquine (HCQ) as loading drugs. Smaller NPs carrying DOX (FeAC-DOX NPs) were loaded into larger NPs containing HCQ (FeAC-DOX@PC-HCQ NPs) by ionic gelation and emulsifying solvent volatilization methods. The physicochemical properties of this Co-NDDS were characterised, followed by in vitro studies of the anticancer effects and mechanisms using two different BC cell lines, MCF-7 cells and MDA-MB-231 cells. The results indicated that the Co-NDDS showcases exemplary physicochemical qualities and encapsulation capacity, facilitating accurate intracellular release through pH-sensitive attributes. Importantly, NPs can significantly increase the in vitro cytotoxicity of co-administered drugs and effectively inhibit the autophagy level of tumour cells. The Co-NDDS constructed in this study provides a promising strategy for the treatment of BC.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2020
·
IF 3.375
Jinwu Wang,Jie Cai,Xingyu Wang,Gaosheng Zhu,Yongzeng Feng,Hua Chen,Leyi Cai
Acute blunt skeletal muscle injury occurs frequently in sports and traffic accidents, and even leads to muscle necrosis and impaired functionality. Current treatment options for muscle injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscles. Tanshinone IIA is extracted from Salvia Miltiorrhizae, which is effective in the treatment of injury repair. But the clinical application of tanshinone IIA is limited due to its low water solubility, low permeability to biofilm and low bioavailability. In this study, tanshinone IIA liposomes were prepared to improve the bioavailability and sustained release of tanshinone IIA. The particle size, dispersion coefficient, zeta potential, encapsulation efficiency (EE) and drug loading (DL) of tanshinone IIA liposomes were 150.67 ± 27.23 nm, 0.20 ± 0.015, -8.73 ± 2.28 mV, 70.32 ± 4.04% and 15.63%, respectively. The results of quantitative real-time polymerase chain reaction (QRT-PCR) showed that tanshinone IIA liposome significantly promoted the expression of vimentin and reduce MHCIIB expression compared with other groups (P < 0.05). Western blotting showed that tanshinone IIA liposome could effectively promote the expression of autophagy-related proteins (VPS34, Beclin 1 and CTSD) and decrease p62 expression levels to treat injured muscle. Through HE, immunohistochemistry, ELISA and serological tests, we found that tanshinone IIA liposome not only effectively promoted the expression of desmin, but also reduced the expression of collagen-I and inhibited the production of pro-inflammatory factors, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) (P < 0.05). In addition, tanshinone IIA liposome therapy significantly reduced the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD) after muscle injury compared with other groups (P < 0.05). In conclusion, tanshinone IIA liposome possesses an effective therapeutic effect on acute blunt muscle injury in rats by augmenting autophagy and alleviating oxidative stress. The continuous release of tanshinone IIA encapsulated by liposomes for disease treatment provide a new idea for the efficient and safe use of drugs with low lipid solubility and bioavailability for the treatment of acute blunt muscle injury and repair of other injuries.
研究领域:
药理学
·
生物技术
·
肌肉骨骼系统
·
药物递送系统
·
损伤修复
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2025
·
IF 6
Yue Wang,Nan Jiang,Shuhan Wu,Guangshuai Lin,Wudang Lu,Bin Shang,Xulong Zhu,Wei Han,Yongmei Chen,Jianhui Li
In the period between surgery and systemic therapy for breast cancer, residual tumor cells may proliferate, leading to tumor recurrence. Additionally, intraoperative wound bleeding may cause surgical failure or the spread of tumor cells. This study introduces an innovative injectable hydrogel composed of oxidized hyaluronic acid (OHA) loaded 5-fluorouracil (5-FU) and N-carboxyethyl chitosan (CEC), designed for intraoperative hemostasis and tumor suppression in intraoperative breast cancer. The CEC/OHA injectable hydrogel was synthesized through a Schiff base reaction between the aldehyde group of OHA and the amino group of CEC, incorporating 5-FU during hydrogel formation. This CEC/OHA injectable hydrogel demonstrated hemostatic effects comparable to gelatin sponges in both an in vivo rat liver hemorrhage model and an in vitro rat tail amputation model. When loaded with 5-FU, the injectable hydrogel effectively inhibited the proliferation of MDA-MB-231 breast cancer cells in vitro , significantly inhibited tumor growth and recurrence in vivo , and did not induce significant damage or inflammatory response in any major organ. This CEC/OHA & 5-FU injectable hydrogel is envisioned as a complementary therapeutic regimen during the intraoperative period in breast cancer surgery to prevent hemostasis and tumor recurrence.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Zhibin Yin,Qian Ji,Di Wu,Ziwei Li,Minfei Fan,Hongxin Zhang,Xiaolong Zhao,Aiguo Wu,Liang Cheng,Leyong Zeng
In order to achieve safe and high-efficient photodynamic therapy (PDT), it was a powerful strategy of constructing O2-generated nanozyme with intelligent “off/on” modulation and enhancement. Herein, a kind of H2O2-responsive nanozyme was developed for off/on modulation and enhancement of magnetic resonance (MR) imaging and PDT, in which great amounts of gold nanoclusters (AuNCs) were loaded into mesoporous silica to form nanoassembly, and manganese dioxide (MnO2) nanosheets were wrapped as switching shield shell (AuNCs@mSiO2@MnO2). In a neutral physiological environment, stable MnO2 shells eliminated singlet oxygen (1O2) generation to switch off PDT and MR imaging. However, in an acidic tumor microenvironment, the MnO2 shell reacted with H2O2, in which MnO2 degradation switched on MR imaging and PDT, and the generated O2 further enhanced PDT. H2O2-responsive MnO2 degradation brought about excellent MR imaging with a longitudinal relaxation rate of 25.31 mM–1 s–1, and simultaneously sufficient O2 generation guaranteed a 74% high 1O2 yield. Under the irradiation of a 635 nm laser, the viability of MDA-MB-435 cells was reduced to 4%, and the tumors completely disappeared, demonstrating strong PDT performance. Therefore, H2O2-responsive AuNCs@mSiO2@MnO2 nanozyme showed excellent off/on modulation and enhancement of MR imaging and PDT and was a promising intelligent nanoprobe for safe and high-efficiency theranostics.
研究领域:
纳米技术
·
生物医学工程
·
癌症研究
·
材料科学
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2021
·
IF 4.219
Qiang Zheng,Yuan Zhang,Zheng Zhao,Haitao Shen,Hongyu Zhao,Min Zhao
Isorhynchophylline (IRN) is an alkaloid with anti-inflammatory and anti-oxidative activities in cardiovascular and brain diseases, but its role in paraquat (PQ)-induced acute kidney injury (AKI) is yet unknown. The model of PQ-induced AKI in rats was established by intraperitoneal injection of PQ (25 mg/kg). We found that the tail vein injection of IRN (4 mg/kg) significantly increased the survival rate of PQ-intoxicated rats. IRN administration alleviated PQ-induced renal injury and renal dysfunction in rats, as evidenced by decreased apoptosis in renal cortex and reduced serum creatinine, serum BUN , and urine NGAL levels. Furthermore, IRN treatment improved the PQ-triggered oxidative stress in renal cortex by increasing the levels of anti-oxidant indicators (SOD activity, GSH/GSSG ratio, levels of Nrf-2, NQO-1, and HO-1 in renal cortex) and decreasing the levels of oxidative stress indexes (ROS and MDA levels in renal cortex). Interestingly, toll-interacting protein (Tollip), a negative regulator of interleukin 1 receptor associated kinase 1 (IRAK1) phosphorylation, was demonstrated to be increased by IRN injection in the renal cortex of PQ-intoxicated rats. In vitro experiments revealed that IRN protected renal tubular epithelial cells against PQ toxicity through suppressing oxidative stress and mitochondrial damage, and these protective effects were reversed by Tollip shRNA . Collectively, the present study demonstrated that IRN ameliorated PQ-induced AKI by attenuating oxidative stress and mitochondrial damage through upregulating Tollip, which provides new insights into the pathogenesis and treatment of PQ poisoning.
研究领域:
药理学
·
毒理学
·
肾脏生理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2020
·
IF 10.257
Bing Han,Lingjun Sha,Xiaomeng Yu,Mei Yang,Ya Cao,Jing Zhao
Breast cancer is the most common malignant disease among women worldwide. Nowadays, combined therapy against several therapeutic targets is becoming a promising treatment to enhance the survival rate of the patients with some lethal subtypes, and also proposes high demand on the discrimination of the co-existing targets in breast cancer. In this work, we designed in situ automatous DNA assembly reaction and applied it for the simultaneous identification of dual therapeutic targets using electrochemical techniques . Taking triple-negative breast cancer cell MDA-MB-231 as a model, chained strand displacement reactions were initiated after the capture probes recognized the surface biomarkers, epidermal growth factor receptor and intercellular adhesion molecule-1, respectively. Then, an increased electrochemical signaling was created to reveal the co-expression of the two targets using quantum dots as electrochemical labeling. Electrochemical results demonstrated high sensitivity and specificity of our method toward the identification of the coexisted therapeutic targets even in the serum samples, which also allowed to monitor the enhanced efficiency of combined therapy. Therefore, our method suggested a potential use in the accurate identification of therapeutic targets in breast cancer that might provide more information to facilitate the combined therapy in clinic.
研究领域:
肿瘤学
·
分子生物学
·
生物技术
·
电化学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA HISTOCHEMICA
·
2019
·
IF 1.719
Yang Wang,Chun Wang,Yue Zhang,Guan Wang,Haitao Yang
Sevoflurane is a widely used inhaled anesthetic , which triggers neuroapoptosis and oxidative damage in the developing central nervous system and cognitive dysfunction later in life. However, no effective therapeutic strategy for sevoflurane-induced deleterious effects is well developed. The purpose of the present study was to explore whether luteoline could attenuate neonatal sevoflurane exposure-triggered neurotoxicity . In this study, six-day-old C57BL/6 mice were pretreated with luteoline (30, 60 mg/kg) intraperitoneally for 30 min before exposed to 3% sevoflurane 6 h consecutively. We first examined the effects of luteoline on hippocampal neuron apoptosis, inflammation and oxidative stress 18 h post anesthesia. The spatial learning and memory performance was measured using Morris water maze test from postnatal day 31 to 38. The results showed that luteoline ameliorated neuronal apoptosis as evidenced by decrease of apoptotic cells, downregulation of the cleavage levels of caspase-3 and PRAP, and inactivation of caspase-3. Moreover, luteoline significantly decreased protein expressions of inflammatory cytokines (IL-1β, IL-18 and TNF-α), inhibited NF-кB/NLRP3 pathway (NF-кB, NLRP3 , ASC and caspase-1) and suppressed NF-кB activity. Our analyses indicated that luteoline had a significant effect on decreasing the contents of ROS and MDA , elevating the activity of SOD, and ultimately improving spatial learning and memory deficits of mice. In summary, our findings confirm that the attenuation of luteoline on sevoflurane-induced spatial learning and memory impairment later is associated with inhibition of hippocampal neuron apoptosis, inflammation and oxidative stress early. Luteoline might be a potential therapeutic for sevoflurane anesthesia-induced neurobehavioral dysfunction.
研究领域:
药理学
·
神经科学
·
麻醉学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2021
·
IF 4.221
Aijing Bi,Zhen Guo,Guocui Yang,Youfang Huang,Zhimin Yin,Lan Luo
Cadmium (Cd) is a highly toxic environmental pollutant, leading to the occurrence and development of multiple neurological diseases. γ-glutamylcysteine (γ-GC) is a dipeptide formed by the condensation of l -glutamic acid and l -cysteine, which has antioxidant, anti-inflammatory, and chelating properties. The purpose of this study is to investigate the effect of γ-GC on Cd-induced apoptosis in PC12 cells. PC12 cells were pretreated with or without γ-GC (2 mM or 4 mM) for 2 h and exposed to Cd (10 μM) for 12 h, and survival, apoptosis, and oxidative stress of PC12 cells were detected after different treatments. The results showed that γ-GC significantly inhibited cell viability reduction, apoptosis, and depolarization of mitochondrial transmembrane potential in Cd-treated PC12 cells, as indicated by CCK-8 assay, flow cytometry, TUNEL staining, and JC-1 detection. Western blot showed that γ-GC down-regulated the ratio of Bax/Bcl-2 and the protein levels of cytosolic cytopigment c, cleaved-caspase-9, cleaved-caspase-3, and cleaved-PARP. Mechanistically, γ-GC suppressed Cd-induced ROS production, MDA accumulation, and GSH depletion, and increased the activity of antioxidant enzymes. Cd-induced activation of MAPK and PI3K/Akt signaling pathways were inhibited by γ-GC treatment, while sustained phosphorylation of JNK, p38, or Akt reversed anti-apoptotic effects of γ-GC. These results suggested that γ-GC inhibited Cd-induced apoptosis in PC12 cells through decreasing oxidative stress and inhibiting the activation of MAPK and PI3K/Akt signaling pathways. γ-GC could be used as a potential protective agent against Cd neurotoxicity.
研究领域:
神经毒理学
·
细胞生物学
·
药理学
·
毒理学
✓ 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）