基于GO@Ag肿瘤靶向近红外光药物控释系统的构建及应用
发布时间：2018-09-01 13:09
【摘要】：光敏感型纳米给药系统凭借其高效、可控、特异性强等优点已经成为生物医学领域研究的热点。构建肿瘤靶向光敏感型纳米给药系统可以有效地调节药物的释放进而增加其对靶组织的选择性、降低化疗药物的全身毒性，从而提高抗肿瘤活性。 本课题构建了一种基于氧化石墨烯/银（GO@Ag）纳米复合材料的阿霉素（DOX）近红外光（NIR）敏感型药物传递系统。首先通过化学淀积法将Ag纳米粒子（~10nm）负载在GO表面得到GO@Ag纳米复合材料，然后将DOX通过酯键连接在GO@Ag上得到GO@Ag-DOX。接着连DSPE-PEG2000-Maleimide（DPM），一方面利用DSPE-PEG2000端的强分散能力增加上述给药体系的水溶性，另一方面利用Maleimide端与NGR发生加成反应将肿瘤靶向基团NGR连接到给药系统GO@Ag-DOX的表面，从而得到肿瘤靶向NIR控释给药系统GO@Ag-DOX-NGR。使用透射电镜、X射线衍射、紫外全波长扫描、傅里叶红外光谱和粒径分析仪等对合成过程及系统形态进行表征。结果表明，成功构建了具有良好水溶性的GO@Ag-DOX-NGR载药系统。 此外考察了GO@Ag-DOX-NGR载药系统在近红外光照射下DOX的释放情况以及其光热转化效应。结果表明，由于近红外光照射下Ag纳米粒的表面等离子共振效应（SPR），DOX的释放显著增加，光照24h后DOX的释放量是无光照组的3.5倍。同时，2W/cm2功率激光照射5min后，GO@Ag-DOX-NGR溶液的温度比GO溶液高约10℃。 体外抗肿瘤活性实验中，以乳腺癌细胞MCF-7为实验对象，考察GO@Ag-DOX-NGR载药系统在近红外光照射下的体外抗肿瘤活性。结果表明，GO@Ag，GO@Ag-NGR无光照时在体外的毒性很小，而光照后由于GO的光热治疗作用对MCF-7细胞的毒性显著增加。载药后光照组比非光照组对MCF-7细胞的生长抑制作用大大提高，而且光照后在细胞核中观察到更多DOX的红色信号，表明NIR光照射对GO@Ag-DOX-NGR在MCF-7细胞中的释放有显著的促进作用。 体内抗肿瘤活性实验中，以S180荷瘤小鼠为模型，主要考察了GO@Ag-DOX-NGR在动物体内的组织分布情况以及体内抑瘤特性，，同时也研究了GO@Ag-DOX-NGR体内X-射线成像情况。结果表明DOX在肿瘤组织的分布增加，而在心脏和肾脏的分布减少；GO@Ag-DOX-NGR具有X光成像对比剂应用的潜力。 综上所述，GO@Ag-DOX-NGR给药系统在体内外均具有靶向性和近红外光敏感性，并且具有X-射线成像功能。近红外敏感型药物传递系统有可能被应用于未来的肿瘤诊断和治疗中。
[Abstract]:Photosensitive drug delivery system has become a hotspot in biomedicine field because of its high efficiency, controllability and specificity. The construction of tumor targeting photo-sensitive drug delivery system can effectively regulate the release of drugs, increase their selectivity to target tissues, reduce the systemic toxicity of chemotherapeutic drugs, and improve the anti-tumor activity. A drug delivery system based on graphene oxide / silver oxide (GO@Ag) nanocomposites for doxorubicin (DOX) near infrared light (NIR) (NIR) was developed. Firstly, Ag nanoparticles (10 nm) were loaded on the surface of GO by chemical deposition method to obtain GO@Ag nanocomposites, and then DOX was bonded to GO@Ag by ester bond to obtain GO@Ag-DOX.. On the one hand, DSPE-PEG2000-Maleimide (DPM), enhanced the water solubility of the drug delivery system by using the strong dispersion ability of the DSPE-PEG2000 terminal, on the other hand, the tumor target group NGR was connected to the surface of the drug delivery system GO@Ag-DOX by the addition reaction between the Maleimide terminal and NGR. Thus, the tumor targeted NIR controlled release drug delivery system GO@Ag-DOX-NGR. was obtained. The synthesis process and system morphology were characterized by transmission electron microscopy (TEM) X-ray diffraction, UV full-wavelength scanning, Fourier transform infrared spectroscopy (FTIR) and particle size analyzer. The results showed that the GO@Ag-DOX-NGR drug carrier system with good water solubility was successfully constructed. In addition, the release of DOX and its photothermal transformation effect of GO@Ag-DOX-NGR drug loading system under near-infrared irradiation were investigated. The results showed that the surface plasmon resonance (SPR) effect of Ag nanoparticles increased significantly under near-infrared irradiation, and the amount of DOX released after 24 hours of irradiation was 3.5 times higher than that in the non-irradiated group. At the same time, the temperature of the Ag-DOX-NGR solution is about 10 鈩
本文编号：2217298
[Abstract]:Photosensitive drug delivery system has become a hotspot in biomedicine field because of its high efficiency, controllability and specificity. The construction of tumor targeting photo-sensitive drug delivery system can effectively regulate the release of drugs, increase their selectivity to target tissues, reduce the systemic toxicity of chemotherapeutic drugs, and improve the anti-tumor activity. A drug delivery system based on graphene oxide / silver oxide (GO@Ag) nanocomposites for doxorubicin (DOX) near infrared light (NIR) (NIR) was developed. Firstly, Ag nanoparticles (10 nm) were loaded on the surface of GO by chemical deposition method to obtain GO@Ag nanocomposites, and then DOX was bonded to GO@Ag by ester bond to obtain GO@Ag-DOX.. On the one hand, DSPE-PEG2000-Maleimide (DPM), enhanced the water solubility of the drug delivery system by using the strong dispersion ability of the DSPE-PEG2000 terminal, on the other hand, the tumor target group NGR was connected to the surface of the drug delivery system GO@Ag-DOX by the addition reaction between the Maleimide terminal and NGR. Thus, the tumor targeted NIR controlled release drug delivery system GO@Ag-DOX-NGR. was obtained. The synthesis process and system morphology were characterized by transmission electron microscopy (TEM) X-ray diffraction, UV full-wavelength scanning, Fourier transform infrared spectroscopy (FTIR) and particle size analyzer. The results showed that the GO@Ag-DOX-NGR drug carrier system with good water solubility was successfully constructed. In addition, the release of DOX and its photothermal transformation effect of GO@Ag-DOX-NGR drug loading system under near-infrared irradiation were investigated. The results showed that the surface plasmon resonance (SPR) effect of Ag nanoparticles increased significantly under near-infrared irradiation, and the amount of DOX released after 24 hours of irradiation was 3.5 times higher than that in the non-irradiated group. At the same time, the temperature of the Ag-DOX-NGR solution is about 10 鈩
本文编号：2217298
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