OBJECTIVE Many drug candidates identified from natural products are poorly water-soluble.The surfactants used to disperse the hydrophobic anticancer drugs in water may cause a serious of acute hypersensitivity reactio...OBJECTIVE Many drug candidates identified from natural products are poorly water-soluble.The surfactants used to disperse the hydrophobic anticancer drugs in water may cause a serious of acute hypersensitivity reactions.Nanotechnology provides an alternative strategy for delivery of anticancer drugs.In the present study,different inorganic nanoparticles are utilized as hydrophobic anticancer drug carriers.METHODS Different inorganic superparamagnetic iron oxide,platinum and gold nanoparticles were synthesized.The hydrophobic anticancer drugs such as curcumin,gambogic acid and doxorubicin(DOX)base were loaded into the porous area or onto the surface of the nanoparticles.Cellular uptake and biocompatibility of nanoparticles were studied in human glioblastoma U-87 MG cells.The anticancer effect of drug loaded nanoparticles was compared with that of free drugs.Photothermal conversion of platinum and gold nanoparticles was studied by irradiation of nanoparticles with a near-infrared laser.RESULTS The synthesized nanoparticles are readily internalized by U-87 MG cells,and the internalized nanoparticles are mainly localized in endosomes/lysosomes in cells.The nanoparticle-based drug carrier provides the aqueous dispersions of the hydrophobic drugs.In endosomes/lysosomes mimicking buffers with a pH of 4.5-5.5,pH-dependent drug release was observed from drug loaded nanoparticles.The intracellular drug content and cytotoxicity are significantly higher for drug loaded nanoparticles than free drug.Photothermal treatment has a synergistic effect on drug′s anticancer activity.CONCLUSION These results suggested inorganic nanoparticles is a promising intracellular carrier for hydrophobic anticancer drugs.展开更多
OBJECTIVE Nanotechnology provides a novel strategy for the delivery of anticancer drugs.METHODS Titanium dioxide coated gold nanostructures(Au/TiO2)was used as the drug carrier for the natural anticancer drug gambogic...OBJECTIVE Nanotechnology provides a novel strategy for the delivery of anticancer drugs.METHODS Titanium dioxide coated gold nanostructures(Au/TiO2)was used as the drug carrier for the natural anticancer drug gambogic acid in order to improve its anticancer effect.Biocompatibility and cellular uptake of Au/TiO2 was studied in human glio⁃blastoma U-87 MG cells.Cell viability was evaluated by ATP assay and calcein AM staining.LysoSensor Green DND-189 and Hoechst 33342 were used to analyze the intracellular location of Au/TiO2.The anticancer effect of gambogic acid loaded nanoparticles was compared with free drug.RESULTS Au/TiO2 was biocompatible,and they were localized at the intracellular acidic compartments of endosomes and lysosomes.The intracellular drug content delivered via Au/TiO2 was 6-fold higher than the free form,thus dramatically enhancing the anticancer effect of gambogic acid.Furthermore,mild photothermal therapy also showed synergistic effect with the drug.CONCLUSION Au/TiO2 is a promising anticancer drug carrier.展开更多
The rapid development of nanotechnology enables the successful application of target drug delivery,which provides new hope for the clinical examination and treatment.In the whole process of drug delivery,we foundcoupl...The rapid development of nanotechnology enables the successful application of target drug delivery,which provides new hope for the clinical examination and treatment.In the whole process of drug delivery,we foundcouple of mechanics problems existed,including the transportation of nanocarriers,the molecular level target and the cellular uptake of nanoparticles.In recent years,we focused on the investigation of diffusion of drug delivery systems in mucus of gastrointestinal(GI)tract and tumor intestinal.We studied the stiffness effect and geometric effect of nanoparticles in cell internalization,and found that the shape,stiffness and adhesion of nanoparticle-based drug carriers affect their transportation in biological tissues.We revealed the internal mechanism with a theoretical model for the diffusion of nanoparticles in an adhesive/nonadhesive polymer network.These findings shed new light on the design of NP-based drug delivery systems targeted to mucosal and tumor sites that possess a fibrous structure/porous medium.展开更多
Exosomes serve as vesicles to deliver protein,lipids,nucleic acids or other cellular components,to neighboring or distant cells.Recent studies have highlighted the potential therapeutic effects of stem cell-derived ex...Exosomes serve as vesicles to deliver protein,lipids,nucleic acids or other cellular components,to neighboring or distant cells.Recent studies have highlighted the potential therapeutic effects of stem cell-derived exosomes on cancer and cardiovascular diseases.Our previous studie.shave investigated the role of stem cell-derived exosomes in cardiac protection.Mesenchymalstem cells released miR-22-enriched exosomes after ischemic preconditioning and these exosomes showed protective effects oncardiomyocytes.MiR-21-conaining exosomes were secreted by H_2O_2-treated cardiac progenitor cells and protected cardiomyocytes from H_2O_2-induced apoptosis.Heat-shock lead to the production ofheat shock factor 1-enriched exosomes from cardiac stem cells,which reducedapoptosis of cardiomyocytes.Given these important effects of exosomes in intercellular communications,exosomes have been proposed as a vector for drug delivery or other therapeutic purposes.However,cells secretea limited number of exosomes,which has hampered the development of exosomes for research and clinical application.Synthetic exosome-mimics by cellextrusion or cell membrane-cloaked nanoparticles,which canbe fabricated on a large-scale,provide novel platforms fordrug delivery.Two Korean groups fabricated exosome-mimetic nanovesicles by extruding monocytes or macrophages through a serial of filters and utilized these exosome-mimetics for the delivery of anti-tumor drug.Recently,cell membrane-cloaked nanoparticles have emergedas a potential tool for drug delivery with the advantages ofimmunocompatibility,stability and targeting capabilityfor the treatment of cancer.In summary,exosomes or exosome-mimics may serve as potential therapeutic tools for the treatment of cardiovascular diseases.展开更多
目的制备负载大蒜新素——二烯丙基三硫化物(DATS)的中空介孔硅纳米微球(HMSNs),并研究其作为下肢缺血性损伤治疗剂的可行性。方法采用选择性蚀刻法合成出HMSNs,同时利用扫描和透射电镜观察微观结构,X射线衍射和动态光散射(DLS)分析理...目的制备负载大蒜新素——二烯丙基三硫化物(DATS)的中空介孔硅纳米微球(HMSNs),并研究其作为下肢缺血性损伤治疗剂的可行性。方法采用选择性蚀刻法合成出HMSNs,同时利用扫描和透射电镜观察微观结构,X射线衍射和动态光散射(DLS)分析理化性质,红细胞溶血实验和细胞毒性实验测试生物安全性。采用吸附法将DATS负载至HMSNs里,获得缓释DATS的纳米颗粒(DATS-HMSNs),并用紫外分光光度法计算并制作DATS的累积释放曲线。将C57BL/6小鼠随机分为四组(假手术组、0.9%氯化钠注射液组、DATS组、DATS-HMSNs组),下肢缺血模型采用股动脉结扎切除法制作。测试各组小鼠肢体缺血前后的运动能力和肌肉内肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、单核细胞趋化蛋-1(MCP-1)、活性氧(ROS)、血小板内皮细胞黏附分子(CD31)、α-平滑肌肌动蛋白(α-SMA)、碱性成纤维细胞生长因子(bFGF)和血管内皮生长因子(VEGF)含量的变化。结果扫描和透射电镜观察可见制备出的HMSNs为中空的球形且粒径均一,DLS结果显示粒径为(226.5±11.8)nm。红细胞溶血实验及细胞毒性实验结果表明HMSNs具备良好的生物相容性。HMSNs对DATS的最大载药率为27.89%,7 d DATS的累积释放率80.12%,21 d可达到97.27%。与对照组比较,DATS-HMSNs用于下肢缺血小鼠后,免疫组化染色发现CD31、α-SMA、bFGF及VEGF的水平增高(P<0.05),ELISA实验发现TNF-α、IL-6、MCP-1和ROS的含量减低(P<0.05),并且缺血后小鼠运动能力恢复满意。结论DATS-HMSNs可以缓慢、持续地释放DATS,为下肢缺血性损伤提供保护作用。展开更多
基金The project supported by Macao Science and Technology Development Fund(014/2014/A1)
文摘OBJECTIVE Many drug candidates identified from natural products are poorly water-soluble.The surfactants used to disperse the hydrophobic anticancer drugs in water may cause a serious of acute hypersensitivity reactions.Nanotechnology provides an alternative strategy for delivery of anticancer drugs.In the present study,different inorganic nanoparticles are utilized as hydrophobic anticancer drug carriers.METHODS Different inorganic superparamagnetic iron oxide,platinum and gold nanoparticles were synthesized.The hydrophobic anticancer drugs such as curcumin,gambogic acid and doxorubicin(DOX)base were loaded into the porous area or onto the surface of the nanoparticles.Cellular uptake and biocompatibility of nanoparticles were studied in human glioblastoma U-87 MG cells.The anticancer effect of drug loaded nanoparticles was compared with that of free drugs.Photothermal conversion of platinum and gold nanoparticles was studied by irradiation of nanoparticles with a near-infrared laser.RESULTS The synthesized nanoparticles are readily internalized by U-87 MG cells,and the internalized nanoparticles are mainly localized in endosomes/lysosomes in cells.The nanoparticle-based drug carrier provides the aqueous dispersions of the hydrophobic drugs.In endosomes/lysosomes mimicking buffers with a pH of 4.5-5.5,pH-dependent drug release was observed from drug loaded nanoparticles.The intracellular drug content and cytotoxicity are significantly higher for drug loaded nanoparticles than free drug.Photothermal treatment has a synergistic effect on drug′s anticancer activity.CONCLUSION These results suggested inorganic nanoparticles is a promising intracellular carrier for hydrophobic anticancer drugs.
基金Macao Science and Technology Development Fund(FDCT)(014/2014/A1)
文摘OBJECTIVE Nanotechnology provides a novel strategy for the delivery of anticancer drugs.METHODS Titanium dioxide coated gold nanostructures(Au/TiO2)was used as the drug carrier for the natural anticancer drug gambogic acid in order to improve its anticancer effect.Biocompatibility and cellular uptake of Au/TiO2 was studied in human glio⁃blastoma U-87 MG cells.Cell viability was evaluated by ATP assay and calcein AM staining.LysoSensor Green DND-189 and Hoechst 33342 were used to analyze the intracellular location of Au/TiO2.The anticancer effect of gambogic acid loaded nanoparticles was compared with free drug.RESULTS Au/TiO2 was biocompatible,and they were localized at the intracellular acidic compartments of endosomes and lysosomes.The intracellular drug content delivered via Au/TiO2 was 6-fold higher than the free form,thus dramatically enhancing the anticancer effect of gambogic acid.Furthermore,mild photothermal therapy also showed synergistic effect with the drug.CONCLUSION Au/TiO2 is a promising anticancer drug carrier.
文摘The rapid development of nanotechnology enables the successful application of target drug delivery,which provides new hope for the clinical examination and treatment.In the whole process of drug delivery,we foundcouple of mechanics problems existed,including the transportation of nanocarriers,the molecular level target and the cellular uptake of nanoparticles.In recent years,we focused on the investigation of diffusion of drug delivery systems in mucus of gastrointestinal(GI)tract and tumor intestinal.We studied the stiffness effect and geometric effect of nanoparticles in cell internalization,and found that the shape,stiffness and adhesion of nanoparticle-based drug carriers affect their transportation in biological tissues.We revealed the internal mechanism with a theoretical model for the diffusion of nanoparticles in an adhesive/nonadhesive polymer network.These findings shed new light on the design of NP-based drug delivery systems targeted to mucosal and tumor sites that possess a fibrous structure/porous medium.
基金supported by NationalNatural Science Foundation of China(81330007NoU1601227)+2 种基金 Science and Technology Programsof Guangdong Province(2014A0505030472015B020225006) Guangzhou Science andTechnology Program(201604010087)
文摘Exosomes serve as vesicles to deliver protein,lipids,nucleic acids or other cellular components,to neighboring or distant cells.Recent studies have highlighted the potential therapeutic effects of stem cell-derived exosomes on cancer and cardiovascular diseases.Our previous studie.shave investigated the role of stem cell-derived exosomes in cardiac protection.Mesenchymalstem cells released miR-22-enriched exosomes after ischemic preconditioning and these exosomes showed protective effects oncardiomyocytes.MiR-21-conaining exosomes were secreted by H_2O_2-treated cardiac progenitor cells and protected cardiomyocytes from H_2O_2-induced apoptosis.Heat-shock lead to the production ofheat shock factor 1-enriched exosomes from cardiac stem cells,which reducedapoptosis of cardiomyocytes.Given these important effects of exosomes in intercellular communications,exosomes have been proposed as a vector for drug delivery or other therapeutic purposes.However,cells secretea limited number of exosomes,which has hampered the development of exosomes for research and clinical application.Synthetic exosome-mimics by cellextrusion or cell membrane-cloaked nanoparticles,which canbe fabricated on a large-scale,provide novel platforms fordrug delivery.Two Korean groups fabricated exosome-mimetic nanovesicles by extruding monocytes or macrophages through a serial of filters and utilized these exosome-mimetics for the delivery of anti-tumor drug.Recently,cell membrane-cloaked nanoparticles have emergedas a potential tool for drug delivery with the advantages ofimmunocompatibility,stability and targeting capabilityfor the treatment of cancer.In summary,exosomes or exosome-mimics may serve as potential therapeutic tools for the treatment of cardiovascular diseases.
文摘目的制备负载大蒜新素——二烯丙基三硫化物(DATS)的中空介孔硅纳米微球(HMSNs),并研究其作为下肢缺血性损伤治疗剂的可行性。方法采用选择性蚀刻法合成出HMSNs,同时利用扫描和透射电镜观察微观结构,X射线衍射和动态光散射(DLS)分析理化性质,红细胞溶血实验和细胞毒性实验测试生物安全性。采用吸附法将DATS负载至HMSNs里,获得缓释DATS的纳米颗粒(DATS-HMSNs),并用紫外分光光度法计算并制作DATS的累积释放曲线。将C57BL/6小鼠随机分为四组(假手术组、0.9%氯化钠注射液组、DATS组、DATS-HMSNs组),下肢缺血模型采用股动脉结扎切除法制作。测试各组小鼠肢体缺血前后的运动能力和肌肉内肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、单核细胞趋化蛋-1(MCP-1)、活性氧(ROS)、血小板内皮细胞黏附分子(CD31)、α-平滑肌肌动蛋白(α-SMA)、碱性成纤维细胞生长因子(bFGF)和血管内皮生长因子(VEGF)含量的变化。结果扫描和透射电镜观察可见制备出的HMSNs为中空的球形且粒径均一,DLS结果显示粒径为(226.5±11.8)nm。红细胞溶血实验及细胞毒性实验结果表明HMSNs具备良好的生物相容性。HMSNs对DATS的最大载药率为27.89%,7 d DATS的累积释放率80.12%,21 d可达到97.27%。与对照组比较,DATS-HMSNs用于下肢缺血小鼠后,免疫组化染色发现CD31、α-SMA、bFGF及VEGF的水平增高(P<0.05),ELISA实验发现TNF-α、IL-6、MCP-1和ROS的含量减低(P<0.05),并且缺血后小鼠运动能力恢复满意。结论DATS-HMSNs可以缓慢、持续地释放DATS,为下肢缺血性损伤提供保护作用。
