本文關(guān)鍵詞： 介孔硅 碳點 近紅外 成像 靶向治療　出處：《中北大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：介孔二氧化硅納米顆粒(MSNs)除了具有表面易功能化、細(xì)胞易于吸收、可生物降解、低毒性和優(yōu)良的生物相容性這些傳統(tǒng)的性能外,還具有獨特的性能,例如高比表面積、大的孔體積、可調(diào)的孔結(jié)構(gòu)和良好的物理化學(xué)穩(wěn)定性等,因此MSNs在生物醫(yī)學(xué)方面的應(yīng)用受到了研究者的特別關(guān)注,已經(jīng)被廣泛應(yīng)用于靶向藥物輸送、診斷、治療等其他的生物醫(yī)學(xué)方面。近二十年來,有大量的研究將熒光蛋白和熒光染料等不同種類的熒光物質(zhì)與介孔硅摻雜,但是這些材料容易光漂白,不適合在血液內(nèi)長期循環(huán)以及實時追蹤。碳點(CDs)作為一種新型的熒光納米材料,其制備方法簡單,原料成本低,具有可調(diào)的發(fā)光范圍、良好的光穩(wěn)定性、易功能化以及良好的生物相容性和水溶性等性質(zhì),和半導(dǎo)體量子點比較,其最大的優(yōu)點就是毒性低,使其在光催化、傳感器、太陽能電池和生物成像等方面具有廣泛的應(yīng)用。本論文將MSNs和CDs復(fù)合得到碳基熒光介孔硅材料,不僅同時具有CDs和MSNs的優(yōu)良性能,還可以作為良好的藥物載體對病變細(xì)胞達(dá)到靶向治療的目的。本論文主要通過兩種不同的方法制備具有不同熒光性能的碳基熒光介孔硅,以實現(xiàn)生物成像與靶向治療一體化,主要工作如下:(1)通過原位合成法將熒光碳點和靶向劑同時作用到MSNs上,此方法制備過程簡單,原料成本低,將葉酸(FA)和氨基化MSNs(MSNs-NH2)混合,一步微波法制備出具有靶向性的熒光介孔硅(FA-CDs-MSNs),其中FA既為CDs來源又可以作為靶向劑。通過系統(tǒng)的研究,其產(chǎn)物具有低毒性、良好的熒光性能和細(xì)胞靶向性,被應(yīng)用于細(xì)胞成像和靶向治療,也被用來區(qū)別癌細(xì)胞和正常細(xì)胞,為了驗證FA-CDs-MSNs對癌細(xì)胞有治療的效果,將其承載藥物阿霉素(DOX),DOX@FA-CDs-MSNs有選擇性地靶向腫瘤組織和抑制癌細(xì)胞的生長,作為藥物載體提高了其藥物利用率和抗癌能力,減小了對其他組織的毒副作用。本論文合成的具有靶向性的的熒光介孔硅為細(xì)胞靶向和治療構(gòu)建了一個新的納米平臺。(2)通過共縮聚法將近紅外碳點(NIR-CDs)合成到MSNs的骨架結(jié)構(gòu)里,再在其表面嫁接線粒體靶向劑(3-羧丙基)三苯基溴化磷(TPP),得到具有線粒體靶向性的近紅外介孔硅(NIR-MSNs-TPP)。首先將近紅外碳點與異氰酸丙基三乙氧基硅烷(IPTS)共軛得到NIR-硅烷,再與TEOS共縮聚反應(yīng)合成近紅外介孔硅(NIR-MSNs),將其氨基化后和TPP通過酰胺反應(yīng)得到最終產(chǎn)物。NIR-CDs在近紅外區(qū)域同時具有激發(fā)和發(fā)射雙光子性能,毒性非常低,可用來雙光子生物成像,近紅外光還具有高組織滲透性和生物友好型等特性,比低滲透性的紫外或者可見光具有非常大的優(yōu)勢,能夠克服紫外可見光在光活化等生物應(yīng)用方面的局限性。將其與MSNs復(fù)合之后,其產(chǎn)物不僅可以用來高滲透雙光子成像還可以用于藥物輸送,將其修飾靶向劑TPP之后,可將藥物輸送至線粒體從而實現(xiàn)更高效的靶向治療。
[Abstract]:In addition to the traditional properties of mesoporous silica nanoparticles, such as easy surface functionalization, easy absorption of cells, biodegradability, low toxicity and excellent biocompatibility, they also have unique properties, such as high specific surface area. Because of its large pore volume, adjustable pore structure and good physical and chemical stability, the application of MSNs in biomedicine has attracted special attention and has been widely used in targeted drug delivery and diagnosis. Treatment and other biomedical aspects. Over the last two decades, a lot of research has been done on doping different kinds of fluorescent substances, such as fluorescent proteins and fluorescent dyes, with mesoporous silicon, but these materials are easy to photobleach. As a new kind of fluorescent nanomaterials, the method of preparation is simple, the cost of raw material is low, the luminescence range is adjustable, and the photostability is good. Easy functionalization and good biocompatibility and water-solubility properties, compared with semiconductor quantum dots, its greatest advantage is low toxicity, making it in photocatalysis, sensors, Solar cells and biometric imaging are widely used. In this paper, MSNs and CDs are combined to produce carbon-based fluorescent mesoporous silicon materials, which not only have the excellent properties of CDs and MSNs, but also have good properties. It can also be used as a good drug carrier for targeted therapy of diseased cells. In this paper, two different methods were used to prepare carbon-based fluorescent mesoporous silicon with different fluorescence properties, so as to realize the integration of biologic imaging and targeted therapy. The main work is as follows: (1) the fluorescent carbon spot and the target agent are simultaneously applied to MSNs by in situ synthesis. The process of preparation is simple and the cost of raw material is low. The fluorescent mesoporous silicon (FA-CDs-MSNs) was prepared by one-step microwave method. FA is both a source of CDs and a targeting agent. Through systematic study, the products have low toxicity, good fluorescence properties and cell targeting. It has been used in cell imaging and targeted therapy, and also used to distinguish cancer cells from normal cells. In order to verify the effect of FA-CDs-MSNs on the treatment of cancer cells, the carrier drug DOXDX FA-CDs-MSNs is selectively targeted at tumor tissues and inhibits the growth of cancer cells. As a drug carrier, the drug utilization rate and anticancer ability are improved. The target fluorescent mesoporous silicon synthesized in this paper has constructed a new nano-platform for cell targeting and treatment. It is synthesized into the skeleton structure of MSNs by means of near infrared carbon dots (NIR-CDss). NIR-silane was obtained by grafting the mitochondrial targeting agent 3-carboxypropyl) triphenyl phosphorous bromide (TPPN) on its surface to obtain near-infrared mesoporous silicon (NIR-MSNs-TPPN) with mitochondrial targeting. First, NIR-silane was obtained by conjugation of near-infrared carbon point with isocyanate triethoxy silane (IPTSs). Near-infrared mesoporous silicon (NIR-MSNsN) was synthesized by copolycondensation with TEOS. The final product, .NIR-CDs, was obtained by amination with TPP through amide reaction. The product, .NIR-CDs, has the properties of excitation and emission of two photons in the near infrared region, and its toxicity is very low, so it can be used for two-photon imaging. Near-infrared light also has high tissue permeability and biological friendliness, and has a great advantage over ultraviolet or visible light with low permeability. It can overcome the limitations of ultraviolet and visible light in biological applications such as photoactivation. When combined with MSNs, the product can be used not only for high permeable two-photon imaging, but also for drug delivery and modification of target agent TPP. Drugs can be transported to mitochondria to achieve more efficient targeted therapy.
【學(xué)位授予單位】：中北大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：TB383.1;TQ460.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 王珊珊;米渭清;朱紅;王芳輝;;一步微波法合成碳點及其熒光性質(zhì)研究[J];光譜學(xué)與光譜分析;2012年10期

，

本文編號：1499159