An acid-sensitive delivery system based on acylhydrazone bond was developed for high loading and efficient delivery of doxorubicin.Doxorubicin(DOX)was covalently combined with dihydrazide adipate to form acid-sensitiv...An acid-sensitive delivery system based on acylhydrazone bond was developed for high loading and efficient delivery of doxorubicin.Doxorubicin(DOX)was covalently combined with dihydrazide adipate to form acid-sensitive hydrazone bond based on Schiff base reaction,then the intermediate was covalently combined with carboxymethyl chitosan through amide bond to form polymeric prodrugs,and nanoparticles were formed through self-assembling.Moreover,the structural and particle properties of CMCS-ADH-DOX were characterized by ultraviolet visible near infrared spectrophotometry(UV),nuclear magnetic resonance spectroscopy(^(1)H-NMR),fourier transform infrared spectroscopy(FT-IR),dynamic light scattering(DLS),and transmission electron microscopy(TEM).The mean diameter of the self-assembled nanoparticles is 165 nm,while the morphology is a relatively uniform spherical shape.Moreover,these DOXloaded nanoparticles showed pH-triggered drug release behavior.Compared with free DOX,CAD NPs showed lower toxic side effects in L929 cells and similar toxicity in 4T1 cells.The experimental results indicate that the CMCS-ADH-DOX nanoparticles may be used as an acid-sensitive targeted delivery system with good application prospect for cancer.展开更多
目的 基于生物信息学和分子对接,探讨栀子柏皮汤治疗炎症性肠病(Inflammatory bowel disease, IBD)的主要活性成分及作用机制。方法 通过中药系统药理学分析平台(Traditional Chinese Medicine Database and Analysis Platform, TCMSP)...目的 基于生物信息学和分子对接,探讨栀子柏皮汤治疗炎症性肠病(Inflammatory bowel disease, IBD)的主要活性成分及作用机制。方法 通过中药系统药理学分析平台(Traditional Chinese Medicine Database and Analysis Platform, TCMSP)和本草组鉴(HERB)数据库筛选“栀子”“甘草”“黄柏”三味药材的有效成分和作用靶点,构建“中药-成分-靶点”网络图。通过基因表达数据库(GEO)和DisGeNET数据库筛选炎症性肠病的相关基因,并用R软件进行数据分析和可视化。通过String平台构建药物和疾病交集靶点的蛋白互作网络(PPI),并利用Cytoscape的MCODE插件筛选核心靶点。使用DAVID平台对核心靶点进行GO和KEGG富集分析。使用AutoDock将核心靶点与活性成分进行分子对接。结果 栀子柏皮汤与炎症性肠病共同作用的目标靶点有13个,GO富集分析得到相关条目49个,KEGG通路富集得到35条信号通路。结论 初步探究了栀子柏皮汤治疗炎症性肠病的潜在靶点和相关通路,栀子柏皮汤中的槲皮素、小檗碱等活性成分,可能通过作用于STAT3、IL-1β和TNF等靶点,调控以TNF、Jak-STAT及NF-κB为代表的信号通路治疗炎症性肠病。展开更多
基金Funded by the Industrial Technology Research Institute of Hubei Provincial Department of Science and Technology(No.2020DEB012)the Hubei Provincial Department of Science and Technology Support Enterprise Technology Innovation Development Project(No.2021BAB119)。
文摘An acid-sensitive delivery system based on acylhydrazone bond was developed for high loading and efficient delivery of doxorubicin.Doxorubicin(DOX)was covalently combined with dihydrazide adipate to form acid-sensitive hydrazone bond based on Schiff base reaction,then the intermediate was covalently combined with carboxymethyl chitosan through amide bond to form polymeric prodrugs,and nanoparticles were formed through self-assembling.Moreover,the structural and particle properties of CMCS-ADH-DOX were characterized by ultraviolet visible near infrared spectrophotometry(UV),nuclear magnetic resonance spectroscopy(^(1)H-NMR),fourier transform infrared spectroscopy(FT-IR),dynamic light scattering(DLS),and transmission electron microscopy(TEM).The mean diameter of the self-assembled nanoparticles is 165 nm,while the morphology is a relatively uniform spherical shape.Moreover,these DOXloaded nanoparticles showed pH-triggered drug release behavior.Compared with free DOX,CAD NPs showed lower toxic side effects in L929 cells and similar toxicity in 4T1 cells.The experimental results indicate that the CMCS-ADH-DOX nanoparticles may be used as an acid-sensitive targeted delivery system with good application prospect for cancer.
文摘目的 基于生物信息学和分子对接,探讨栀子柏皮汤治疗炎症性肠病(Inflammatory bowel disease, IBD)的主要活性成分及作用机制。方法 通过中药系统药理学分析平台(Traditional Chinese Medicine Database and Analysis Platform, TCMSP)和本草组鉴(HERB)数据库筛选“栀子”“甘草”“黄柏”三味药材的有效成分和作用靶点,构建“中药-成分-靶点”网络图。通过基因表达数据库(GEO)和DisGeNET数据库筛选炎症性肠病的相关基因,并用R软件进行数据分析和可视化。通过String平台构建药物和疾病交集靶点的蛋白互作网络(PPI),并利用Cytoscape的MCODE插件筛选核心靶点。使用DAVID平台对核心靶点进行GO和KEGG富集分析。使用AutoDock将核心靶点与活性成分进行分子对接。结果 栀子柏皮汤与炎症性肠病共同作用的目标靶点有13个,GO富集分析得到相关条目49个,KEGG通路富集得到35条信号通路。结论 初步探究了栀子柏皮汤治疗炎症性肠病的潜在靶点和相关通路,栀子柏皮汤中的槲皮素、小檗碱等活性成分,可能通过作用于STAT3、IL-1β和TNF等靶点,调控以TNF、Jak-STAT及NF-κB为代表的信号通路治疗炎症性肠病。