發(fā)布時(shí)間：2018-09-01 13:09

【摘要】：光敏感型納米給藥系統(tǒng)憑借其高效、可控、特異性強(qiáng)等優(yōu)點(diǎn)已經(jīng)成為生物醫(yī)學(xué)領(lǐng)域研究的熱點(diǎn)。構(gòu)建腫瘤靶向光敏感型納米給藥系統(tǒng)可以有效地調(diào)節(jié)藥物的釋放進(jìn)而增加其對(duì)靶組織的選擇性、降低化療藥物的全身毒性，從而提高抗腫瘤活性。 本課題構(gòu)建了一種基于氧化石墨烯/銀（GO@Ag）納米復(fù)合材料的阿霉素（DOX）近紅外光（NIR）敏感型藥物傳遞系統(tǒng)。首先通過(guò)化學(xué)淀積法將Ag納米粒子（~10nm）負(fù)載在GO表面得到GO@Ag納米復(fù)合材料，然后將DOX通過(guò)酯鍵連接在GO@Ag上得到GO@Ag-DOX。接著連DSPE-PEG2000-Maleimide（DPM），一方面利用DSPE-PEG2000端的強(qiáng)分散能力增加上述給藥體系的水溶性，另一方面利用Maleimide端與NGR發(fā)生加成反應(yīng)將腫瘤靶向基團(tuán)NGR連接到給藥系統(tǒng)GO@Ag-DOX的表面，從而得到腫瘤靶向NIR控釋給藥系統(tǒng)GO@Ag-DOX-NGR。使用透射電鏡、X射線衍射、紫外全波長(zhǎng)掃描、傅里葉紅外光譜和粒徑分析儀等對(duì)合成過(guò)程及系統(tǒng)形態(tài)進(jìn)行表征。結(jié)果表明，成功構(gòu)建了具有良好水溶性的GO@Ag-DOX-NGR載藥系統(tǒng)。 此外考察了GO@Ag-DOX-NGR載藥系統(tǒng)在近紅外光照射下DOX的釋放情況以及其光熱轉(zhuǎn)化效應(yīng)。結(jié)果表明，由于近紅外光照射下Ag納米粒的表面等離子共振效應(yīng)（SPR），DOX的釋放顯著增加，光照24h后DOX的釋放量是無(wú)光照組的3.5倍。同時(shí)，2W/cm2功率激光照射5min后，GO@Ag-DOX-NGR溶液的溫度比GO溶液高約10℃。 體外抗腫瘤活性實(shí)驗(yàn)中，以乳腺癌細(xì)胞MCF-7為實(shí)驗(yàn)對(duì)象，考察GO@Ag-DOX-NGR載藥系統(tǒng)在近紅外光照射下的體外抗腫瘤活性。結(jié)果表明，GO@Ag，GO@Ag-NGR無(wú)光照時(shí)在體外的毒性很小，而光照后由于GO的光熱治療作用對(duì)MCF-7細(xì)胞的毒性顯著增加。載藥后光照組比非光照組對(duì)MCF-7細(xì)胞的生長(zhǎng)抑制作用大大提高，而且光照后在細(xì)胞核中觀察到更多DOX的紅色信號(hào)，表明NIR光照射對(duì)GO@Ag-DOX-NGR在MCF-7細(xì)胞中的釋放有顯著的促進(jìn)作用。 體內(nèi)抗腫瘤活性實(shí)驗(yàn)中，以S180荷瘤小鼠為模型，主要考察了GO@Ag-DOX-NGR在動(dòng)物體內(nèi)的組織分布情況以及體內(nèi)抑瘤特性，，同時(shí)也研究了GO@Ag-DOX-NGR體內(nèi)X-射線成像情況。結(jié)果表明DOX在腫瘤組織的分布增加，而在心臟和腎臟的分布減少；GO@Ag-DOX-NGR具有X光成像對(duì)比劑應(yīng)用的潛力。 綜上所述，GO@Ag-DOX-NGR給藥系統(tǒng)在體內(nèi)外均具有靶向性和近紅外光敏感性，并且具有X-射線成像功能。近紅外敏感型藥物傳遞系統(tǒng)有可能被應(yīng)用于未來(lái)的腫瘤診斷和治療中。
[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

本文編號(hào)：2217298