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無機(jī)微納米材料的仿生合成及其在藥物輸送和光催化領(lǐng)域的潛在應(yīng)用

發(fā)布時(shí)間:2018-08-13 13:39
【摘要】:惡性腫瘤作為臨床上最難治愈的疾病之一,嚴(yán)重威脅著全世界人民的生命安全。目前對(duì)其常規(guī)的療法僅限于手術(shù)治療、化學(xué)治療和放射治療,但這些方法存在副作用較大、靶向性低、易產(chǎn)生抗藥性等缺點(diǎn)?鼓[瘤靶向制劑的出現(xiàn),克服了以上常規(guī)療法的不足,可以減小對(duì)其他正常組織的毒副作用、降低給藥量以及提高藥效。無機(jī)納米材料具有諸多優(yōu)異的物理化學(xué)性能,被廣泛用于藥物輸送、熒光標(biāo)記、鋰電池、催化、污水處理、傳感和化學(xué)儲(chǔ)能等。近年來,利用生物礦化機(jī)制進(jìn)行仿生合成是的材料化學(xué)領(lǐng)域的熱點(diǎn),但是對(duì)于材料的結(jié)構(gòu)、尺寸、形貌和晶型等與其細(xì)胞生物學(xué)效應(yīng)之間的關(guān)系研究較少。未來應(yīng)加強(qiáng)在該方向的研究,并在實(shí)際應(yīng)用之前評(píng)估其科學(xué)性、安全性和有效性,為無機(jī)納米材料的設(shè)計(jì)合成與其在生物醫(yī)學(xué)領(lǐng)域的應(yīng)用提供理論依據(jù)。本論文主要開展了以下幾方面的研究:利用花粉溶出物作為有機(jī)基質(zhì),合成了多孔空殼碳酸鈣材料,通過多種不同手段對(duì)樣品的形貌和性質(zhì)進(jìn)行了測(cè)試和表征。結(jié)果表明,所合成材料粒徑均一,存在大量介孔,且內(nèi)部為中空結(jié)構(gòu),具有較大的比表面積,這些性質(zhì)都有助于提高材料的藥物負(fù)載能力。以抗腫瘤藥物鹽酸阿霉素作為模型,對(duì)所合成的CaCO3材料進(jìn)行了體外藥物負(fù)載-控釋實(shí)驗(yàn)。實(shí)驗(yàn)結(jié)果表明,合成的CaCO3材料對(duì)藥物具有高的負(fù)載能力,達(dá)到了91.4%?蒯寣(shí)驗(yàn)結(jié)果表明,實(shí)驗(yàn)合成的CaCO3具有pH敏感性,在弱酸性條件下,能夠逐漸分解,繼而釋放出藥物,而它在中性和弱堿性條件下是很難分解的。由此,可減少在正常細(xì)胞周圍釋放。研究表明,所合成的材料可以對(duì)抗腫瘤藥物進(jìn)行持續(xù)可控釋放,延長藥物的釋放時(shí)間,減少給藥次數(shù),這一結(jié)果也為材料的細(xì)胞活性實(shí)驗(yàn)提供了重要的依據(jù)。細(xì)胞生物學(xué)測(cè)試結(jié)果顯示,將DOX負(fù)載于材料后,藥物的特異性顯著增加,可提高至純藥的17倍。體外細(xì)胞實(shí)驗(yàn)證實(shí),合成的多孔空殼碳酸鈣可以通過胞吞作用進(jìn)入腫瘤細(xì)胞內(nèi)部,進(jìn)而釋放出藥物。綜上所述,實(shí)驗(yàn)合成的多孔空殼碳酸鈣在抗腫瘤藥物負(fù)載和臨床腫瘤治療領(lǐng)域有著廣闊的潛在應(yīng)用前景。用液-液界面反應(yīng)的簡(jiǎn)便方法合成了立方雙層殼碳酸鈣和立方空殼碳酸鈣,本文探究了其反應(yīng)物濃度和反應(yīng)溫度對(duì)其形貌的影響。文中用場(chǎng)發(fā)射掃描電鏡、透射電鏡等對(duì)其進(jìn)行表征,并對(duì)其形成機(jī)理進(jìn)行初步推測(cè)。用溶劑熱法合成了具有介孔結(jié)構(gòu)的花狀硫化銅。測(cè)試結(jié)果表明,實(shí)驗(yàn)合成的CuS形貌大小均一,由數(shù)十片薄片組成,粒徑約為340 nm。該片組裝花狀CuS半導(dǎo)體材料具有優(yōu)異的光學(xué)性能,其間接半導(dǎo)體和直接半導(dǎo)體禁帶寬度分別為1.36 eV、2.14 eV。因其具有較大的比表面積和孔容,使得樣品表面存在更多的活性位點(diǎn),在催化反應(yīng)中表現(xiàn)出優(yōu)異的光催化活性,這使其在催化領(lǐng)域具有廣闊的潛在應(yīng)用前景。該研究以亞甲基藍(lán)為有機(jī)污染物模型,實(shí)驗(yàn)結(jié)果為其進(jìn)一步用于降解其他有機(jī)毒性污染物提供了實(shí)驗(yàn)依據(jù)及理論指導(dǎo)。
[Abstract]:As one of the most difficult diseases to cure in clinic, malignant tumors seriously threaten the lives of people all over the world. At present, the conventional therapy is limited to surgical treatment, chemotherapy and radiotherapy, but these methods have some disadvantages, such as large side effects, low targeting, easy to produce drug resistance and so on. Inorganic nanomaterials have many excellent physical and chemical properties and are widely used in drug delivery, fluorescence labeling, lithium batteries, catalysis, sewage treatment, sensing and chemical energy storage. In recent years, biomineralization mechanisms have been used to improve the performance of inorganic nanomaterials. Biomimetic synthesis is a hotspot in the field of material chemistry, but little research has been done on the relationship between the structure, size, morphology and crystal form of materials and their cellular biological effects. In this paper, the porous and hollow calcium carbonate materials were synthesized by using pollen extract as organic matrix. The morphology and properties of the samples were tested and characterized by various means. The results showed that the synthesized materials had uniform particle size and existed. A large number of mesoporous materials with hollow structure and large specific surface area can improve the drug loading ability of the materials. The drug loading-controlled release experiments of the synthesized CaCO3 materials were carried out in vitro with the antitumor drug adriamycin hydrochloride as the model. The results showed that the synthesized CaCO3 materials had high drug loading-controlled release ability. The results of controlled-release experiments showed that the CaCO3 synthesized in this experiment was pH-sensitive and could decompose gradually under weak acidic conditions, and then release the drug. However, it was difficult to decompose under neutral and weak alkaline conditions. Thus, the release around normal cells could be reduced. The results of cytobiological assay showed that the specificity of the drug was significantly increased when DOX was loaded on the material, which was 17 times higher than that of the pure drug. In summary, the experimental synthesis of porous calcium carbonate has broad potential applications in the fields of antitumor drug loading and clinical tumor therapy. Cubic bicapsular carbonate was synthesized by a simple method of liquid-liquid interface reaction. Calcium and cubic hollow calcium carbonate were characterized by field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). Flower copper sulfide with mesoporous structure was synthesized by solvothermal method. The fabricated flower-like CuS semiconductors have excellent optical properties. The band gap of indirect and direct semiconductors are 1.36 eV and 2.14 eV, respectively. Because of their large specific surface area and pore volume, more active sites are found on the surface of the sample. The photocatalytic activity of methylene blue is excellent, which makes it have a broad potential application in the catalytic field. Methylene blue is used as organic pollutant model in this study. The experimental results provide experimental basis and theoretical guidance for its further application in the degradation of other organic toxic pollutants.
【學(xué)位授予單位】:河南師范大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:TB383.1

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