本文選題：納米探針 + 分子成像��； 參考：《長春工業(yè)大學(xué)》2017年碩士論文

【摘要】：納米材料在生物醫(yī)學(xué)應(yīng)用領(lǐng)域具有獨(dú)特的優(yōu)勢,如可控合成、易于表面功能化修飾、長的體內(nèi)循環(huán)時間、可以負(fù)載多功能物質(zhì)于一身等,因此,納米材料已廣泛應(yīng)用于生物成像、臨床診斷和治療等領(lǐng)域。本論文面向惡性腫瘤早期診斷的重大需求,從腫瘤的同時診斷和治療角度出發(fā),設(shè)計制備了兩種新型的多功能納米探針,探索了其在T1/T2-MR/CT多模式成像和成像介導(dǎo)的腫瘤光熱治療中的應(yīng)用。研究內(nèi)容為以下兩部分:1、設(shè)計制備了封裝Gd和Dy離子的牛血清白蛋白(BSA)納米粒子,利用多巴胺的自聚合特性在粒子表面原位聚合生長聚多巴胺層(PDA),然后通過化學(xué)鍵將葉酸(FA)修飾到粒子表面,成功獲得了具有腫瘤靶向性的診療探針BSA:Gd,Dy@PDA-FA。該探針的設(shè)計基于以下幾點(diǎn):稀土元素Gd具有順磁性,Dy具有較強(qiáng)的X-射線吸收能力,可以作為MRI/CT成像探針的基質(zhì)。聚多巴胺在近紅外區(qū)有強(qiáng)的吸收,在808 nm激光器照射下能把光能轉(zhuǎn)換成熱能進(jìn)行光熱治療。葉酸受體在腫瘤表面是過表達(dá)的,所以利用葉酸對葉酸受體的高度親和性,可將探針靶向至腫瘤。研究結(jié)果表明,BSA:Gd,Dy@PDA-FA診療探針具有優(yōu)異的穩(wěn)定性,通過細(xì)胞毒性和組織切片分析證實(shí)此探針毒性相對較低。此探針?biāo)芤涸贜IR激光照射5min后能升高溫度到60℃,這種高的光熱轉(zhuǎn)換效率說明我們制備的探針能夠進(jìn)行腫瘤的光熱治療。經(jīng)此探針培育后,腫瘤細(xì)胞在激光照射后存活率下降到8%。此外,BSA:Gd,Dy@PDA-FA診療探針具有較高的r1值(9.47mM-1 s-1)、r2值(18.42 mM-1 s-1)和X-射線吸收系數(shù)(51.8 HU g-1),可以進(jìn)行T1/T2-MR/CT多模式成像。2、稀土氟化物納米粒子由于具有良好的光穩(wěn)定性、低的生物毒性、易于調(diào)控的粒子尺寸和形貌,通常被用作多模式成像探針的載體材料。我們通過熱解法制備了超小的、粒徑可控的Dy摻雜NaGd F_4納米粒子,通過配體交換法將兩親性聚乙烯吡咯烷酮(PVP)修飾到粒子表面,獲得了水溶性的T1/T2-MR/CT多模式成像探針PVP-NaGdF_4:Dy。從細(xì)胞、組織器官到整體生物水平上的系統(tǒng)研究證實(shí)了此成像探針具有良好的生物相容性。體內(nèi)分布代謝研究顯示此探針進(jìn)入小鼠體內(nèi)之后主要累積在肝和脾中,注射30天后基本能全部排出體外,避免了在體內(nèi)的長期毒性。該成像探針的r1值(6.15mM-1 s-1)、r2值(13.82mM-1 s-1)和X-射線吸收能力(48.5HU g-1)明顯高于臨床上常用的成像探針Gd-DTPA和碘比醇。小鼠體內(nèi)MR和CT成像結(jié)果表明此成像探針在肝和脾有明顯的對比增強(qiáng)效果。重要的是,此成像探針實(shí)現(xiàn)了腫瘤成像。
[Abstract]:Nanomaterials have unique advantages in biomedical applications, such as controllable synthesis, easy surface functionalization, long internal circulation time, and the ability to load multifunctional substances in one body. Nanomaterials have been widely used in biological imaging, clinical diagnosis and treatment. In order to meet the great need of early diagnosis of malignant tumors, two novel multifunctional nanoprobes were designed and prepared from the point of view of simultaneous diagnosis and treatment of malignant tumors. Its application in T1/T2-MR/CT multi-mode imaging and imaging-mediated photothermal therapy was explored. The BSA nanoparticles encapsulated in Gd and Dy ions were designed and prepared in the following two parts: 1. The dopamine layer PDA-PDA-FAA was prepared by in-situ polymerization of dopamine on the surface of particles by self-polymerization of dopamine, and then modified to the surface of the particles by chemical bonds. A tumor targeting diagnostic probe, BSA: GdCy DyPDA-FA-FA-FA-FA-FA-PDA-FA-PDA-FA-Dy was successfully obtained. The design of the probe is based on the following points: the rare earth element Gd has the strong X- ray absorption ability of paramagnetic Dy and can be used as the substrate of the MRI/CT imaging probe. Poly (dopamine) has strong absorption in near infrared region and can convert light energy into heat energy for photothermal therapy under 808 nm laser irradiation. Folic acid receptor is overexpressed on the surface of tumor, so the high affinity of folic acid to folate receptor can target the tumor. The results showed that BSA: GdDy @ PDA-FA probe had excellent stability, and was proved to be relatively low by cytotoxicity and histological analysis. This probe solution can raise the temperature to 60 鈩，

本文編號：1869255