肿瘤靶向pH响应药物递送-成像体系的合成与控制释放研究
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摘要
对聚烯丙基胺修饰合成了一种苯硼酸靶向的聚合物配体:聚烯丙基胺/马来酸酐-聚乙二醇-硫辛酸-苯硼酸(PAH/SA-PEG-LA-PBA),共轭作用在ZnO、CdTe/CdS量子点表面,连接抗癌药物阿霉素后形成苯硼酸靶向-示踪诊疗一体体系:ZnO、CdTe/CdS@(PAH/SA-PEG-LA-PBA)-DOX(量子点的荧光可示踪/显像药物递送过程),核磁共振(~1H-NMR)测试表明成功合成了(PAH/SA-PEG-LA-PBA)聚合物,透射电镜(TEM)测得该体系呈规整球形且分布均匀,平均粒径约30 nm;紫外-可见光谱(UV-Vis)和荧光谱图显示该体系具有ZnO、CdTe/CdS量子点的吸收峰,还出现了较强的荧光发射峰,由此说明了苯硼酸靶向的诊疗示踪一体体系的成功制得,负载阿霉素的纳米粒子的载药量为80%.体外释放研究表明,pH 5.0时药物释放速度比pH 7.4时快,48 h后累计释放率达87.1%.因此,该pH响应性纳米颗粒作为抗癌药物载体具有潜在的应用价值.
A phenylboronic acid-targeted polymer ligand was synthesized by modification of polyallylamine:polyallylamine/maleic anhydride-polyethylene glycol-lipoic acid-phenylboronic acid(PAH/SA-PEG-LA-PBA), which was conjugated to the surface of ZnO and CdTe/CdS quantum dots and connected with the anticancer drug doxorubicin to form a system of phenylborate targeting-trace diagnosis and treatment: ZnO,CdTe/CdS@(PAH/SA-PEG-LA-PBA)-DOX(fluorescence traceable/developing drug delivery process for quantum dots), nuclear magnetic resonance(~1H-NMR) analysis showed that the(PAH/SA-PEG-LA-PBA) polymer was successfully synthesized. The system was spherical and uniform in distribution by TEM. The average particle size was about 30 nm, UV-Vis and the fluorescence spectrum shows that the system has characteristic absorption peaks of ZnO. CdTe/CdS quantum dots and a strong fluorescence emission peak appears, This shows the successful system of phenylboronic acid-targeted diagnosis and tracing integrated system, The drug loading of the doxorubicin-loaded nanoparticles was 80%, In vitro release studies showed that the drug release rate was faster at pH 5.0 than at pH 7.4, and the cumulative release rate was 87.1% after 48 h, Therefore, the pH responsive nanoparticle has potential application value as an anticancer drug carrier.
A phenylboronic acid-targeted polymer ligand was synthesized by modification of polyallylamine:polyallylamine/maleic anhydride-polyethylene glycol-lipoic acid-phenylboronic acid(PAH/SA-PEG-LA-PBA), which was conjugated to the surface of ZnO and CdTe/CdS quantum dots and connected with the anticancer drug doxorubicin to form a system of phenylborate targeting-trace diagnosis and treatment: ZnO,CdTe/CdS@(PAH/SA-PEG-LA-PBA)-DOX(fluorescence traceable/developing drug delivery process for quantum dots), nuclear magnetic resonance(~1H-NMR) analysis showed that the(PAH/SA-PEG-LA-PBA) polymer was successfully synthesized. The system was spherical and uniform in distribution by TEM. The average particle size was about 30 nm, UV-Vis and the fluorescence spectrum shows that the system has characteristic absorption peaks of ZnO. CdTe/CdS quantum dots and a strong fluorescence emission peak appears, This shows the successful system of phenylboronic acid-targeted diagnosis and tracing integrated system, The drug loading of the doxorubicin-loaded nanoparticles was 80%, In vitro release studies showed that the drug release rate was faster at pH 5.0 than at pH 7.4, and the cumulative release rate was 87.1% after 48 h, Therefore, the pH responsive nanoparticle has potential application value as an anticancer drug carrier.
引文
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[14] HINDS K A,HILL J M,SHAPIRO E M,et al.Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells [J].Blood,2003,102(3):867-872.
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[17] SAMANTA A,DENG Z,LIU Y.Aqueous synthesis of glutathione-capped CdTe/ZnS/ZnS and CdTe/ZnSe/ZnS core/shell/shell nanocrystal heterostructures [J].Langmuir,2012,28(21):8205-8215.
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