Acta Biomaterialia
·
2020
·
IF 7.242
Zhaoming Guo,Ye Liu,Xiao Cheng,Dong Wang,Shubin Guo,Mingli Jia,Kun Ma,Changhao Cui,Li Wang,Hao Zhou
The heat shock response (HSR) induced by photothermal therapy (PTT), which can cause tumor cells to resist apoptosis, has increasingly attracted the attention of researchers. Synergistic treatment of tumors using multiple means to improve therapeutic efficiency would be a promising strategy for effective cancer treatment. In this study, a cancer cell membrane-camouflaged nanocarrier was developed and loaded with tellurium (Te) and cantharidin (CTD) for efficient combinatorial therapy. The designed nanoparticles ( [email protected] ) used a 4T1 cell membrane coating as the shell with homologous targeting capability, CTD as an the HSR inhibitor and antitumor drug, and Te as a PTT and photodynamic therapy (PDT) photosensitizer . An in vivo study indicated that the tumor inhibition rate of this combinatorial therapy could reach approximately 82.3% in 4T1 mammary tumor models. This study suggested that [email protected] , as a versatile biomimetic nanoplatform, provides a new alternative for more precise and effective tumor treatment. Statement of significance In this work, we constructed cell membrane-coated biomimetic nanoparticles ( [email protected] ) to suppress cancer effectively through synergistic treatment. The developed [email protected] nanoparticles presented strong homologous targeting capabilities. The encapsulated Te triggered PDT and PPT under the near-infrared laser irradiation. Subsequently, the PTT triggered the release of CTD, which could suppress the HSR of tumor and achieve chemotherapy. In addition, due to the presence of outer cell membrane coating, these [email protected] nanoparticles showed good biocompatibility to healthy cells.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Qiyi Wang,Weina Cheng,Tianmu He,Shan Li,Jingwen Ao,Yanmei He,Cancan Duan,Xiaofei Li,Jianyong Zhang
The hepatotoxicity mechanism of cantharidin (CTD), a major active component of Mylabris was explored based on liver lipidome alterations and spatial distributions in female and male rats using lipidomics and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). After oral CTD exposure, the livers of female rats were screened for 104 differential lipids including lysophosphatidylethanolamine(LysoPE)(20:2/0:0) and diacylglycerol(DG)(18:2/22:4), whereas the livers of male rats were screened for 76 differential lipids including fatty acid(FA)(24:6) and DG(18:0/22:4). According to the MALDI-MSI results, female rats exhibited 12 differential lipids with alteration in the abundance and spatial distribution of phosphatylcholine(PC), phosphatidylethanolamine(PE), lysophosphatidylcholine(LysoPC), and LysoPE in the liver lesion area. On the other hand, male rats exhibited 8 differential lipids with changes in the abundance and spatial distribution of PC, PE, and FA in the liver lesion area. The lipidomics- and MALDI-MSI-detected differential lipids strongly disrupted glycerophospholipid metabolism in both female and male rats. Additionally, phosphatidate phosphatase ( Lipin1), choline/ethanolamine phosphotransferase 1 (CEPT1), and phosphatidylethanolamine N-methyltransferase (PEMT) were screened to distinguish CTD hepatoxicity in female and male rats. Western blotting analysis demonstrated a significant elevation in Lipin1 expression in female and male rat livers, accompanied by a decrease in PEMT expression. Furthermore, CEPT1 expression increased significantly in female rat livers and decreased significantly in male rat livers. These findings suggested that CTD could disrupt lipid metabolism in a gender-specific manner. Moreover, the combination of lipidomics and MALDI-MSI could offer valuable insights into CTD-induced hepatotoxicity in rats.
研究领域:
药理学
·
毒理学
·
分析化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2021
·
IF 2.882
Shuang Sun,Eryu Shang,Aixia Ju,Yalun Li,Qian Wu,Qiuhong Li,Yang Yang,Yuyan Guo,Dayu Yang,Shaowa Lv
Aim Cantharidin (CTD), the major component of the anti-cancer medicine obtained from Mylabris cichorii , exerts good inhibitory effects on several cancers, such as liver and breast cancer. However, owing to its toxicity, its oral administration can cause various adverse effects, limiting its clinical applications. Therefore, the development of a novel nano-drug delivery system for CTD would be highly beneficial. Methods A nanostructured lipid carrier (NLC) was designed to actively target CTD to tumor cells using a hyaluronic acid (HA)-decorated copolymer (mPEG-NH 2 ); the NLCs were called HA-mPEG-CTD-NLC. HA-mPEG was synthesized using amidation, and HA-mPEG-CTD-NLC was generated through ultrasonic emulsification in water. The mean hydrodynamic diameter of the particles was approximately 119.3 nm. Results Pharmacokinetic studies revealed that the half-life of HA-mPEG-CTD-NLC and its area under the curve were higher than those of a CTD solution. Further, the plasma clearance rate of HA-mPEG-CTD-NLC was 0.41 times that of the CTD solution, implying a significantly prolonged drug retention time in vivo . Fluorescence in vivo endo -microscopy and optical in vivo imaging revealed that HA-mPEG-CTD-NLC had superior cytotoxicity and targeting efficacy against SMMC-7721 cells. An evaluation of the in vivo anti-tumor activity showed that HA-mPEG-CTD-NLC significantly inhibited tumor growth and prolonged survival in tumor-bearing mice, with a tumor inhibition rate of 65.96%. Conclusions Our results indicate that HA-mPEG-CTD-NLC may have great potential in liver cancer-targeted therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Thoracic Cancer
·
2020
·Vol. 11
·期 6
·1476-1486
·
IF 2.61
Kun Zheng,Runze Chen,Yanxue Sun,Zhenquan Tan,Ye Liu,Xiao Cheng,Junke Leng,Zhaoming Guo,Pengcheng Xu
Background Although photodynamic therapy (PDT) has emerged as a potential alternative to conventional chemotherapy, the low reactive oxygen species (ROS) yield of the photosensitizer such as TiO 2 nanoparticles has limited its application. In addition, it is difficult to achieve effective tumor treatment with a single tumor therapy. Methods We used TiOx nanocomposite (YSA-PEG-TiO X ) instead of TiO 2 as a photosensitizer to solve the problem of insufficient ROS generation in PDT. Benefiting from the desired mesoporous structure of TiOx, Cantharidin (CTD), one of the active components of mylabris, is loaded into TiOx for targeted combination of chemotherapy and PDT. The cellular uptake in human non-small cell lung carcinoma cell line (A549) and human normal breast cell line (MCF 10A) was evaluated by confocal microscopy. in vitro cytotoxicity was evaluated using Cell Counting Kit-8 assay. The ROS was detected via a chemical probe DCFH-DA and the photodynamic treatment effect of YSA-PEG-TiOx was further evaluated by a living-dead staining. The cell apoptosis was detected by the flow cytometry. Results Our findings showed that the modification of YSA peptide improved the cytotoxicity of YSA-PEG-TiO X /CTD to EphA2 overexpressing A549 non-small cell lung cancer (NSCLC) than non-YSA modified counterparts. In addition, TiOx generated adequate ROS under X-ray irradiation to further kill cancer cells. Flow analysis results also proved the superiority of this combined treatment. Conclusions YSA-PEG-TiO X nanoparticles could significantly increase ROS production under X-ray exposure and provide a new drug delivery nanocarrier for CTD in combination with PDT to achieve effective NSCLC treatment.
研究领域:
纳米技术
·
癌症研究
·
治疗学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2020
·Vol. 40
·期 8
·1153-1161
·
IF 2.997
Zhang Youyou,Yu Yalei,Zhang Jie,Guan Chuhuai,Liu Liang,Ren Liang
Early diagnosis of cantharidin-induced myocardial injury is the key to reduce the fatality rate in clinical practice. The purpose of the present study was to explore biomarkers that can be used for the prediction and diagnosis of cantharidin-induced myocardial injury. Of 65 male Sprague-Dawley rats weighing 200-230 g, 25 rats were divided into five groups according to the administration dose of cantharidin (0, 1.34, 2.67, 4 and 5.34 mg/kg; n = 5 per group) and the other 40 rats were treated with 2.67 mg/kg cantharidin and divided into nine groups according to the administration time (0, 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours; n = 4 per group). Pathological changes of hypoxia, necrosis and inflammation were confirmed in heart samples that were exposed to cantharidin by hematoxylin-eosin staining and overall scores of pathological changes among heart samples in cantharidin exposure groups showed an increasing trend compared with in the control group. Coexpression of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α) and caspase9 was shown in the myocardium by immunofluorescence staining. Western blotting results showed that expression of VEGF, HIF-1α and caspase9 in cantharidin-treated rat hearts showed an increasing trend compared with in the control group. Results of enzyme-linked immunosorbent assay suggested that plasma levels of troponin T (TN-T), VEGF and HIF-1α were elevated at different intervals after cantharidin administration, and VEGF and HIF-1α had a significant linear relationship with TN-T that was verified by multiple linear regression analysis. Preliminary results serve to illustrate that TN-T, VEGF and HIF-1α might be valuable molecular markers in cantharidin-induced myocardial injury and that diagnostic accuracy needs to be studied further.
✓ 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）