發(fā)布時間：2019-05-12 00:41

【摘要】：目前,如何實現(xiàn)藥物的可控釋放及對藥物傳遞過程的追蹤,已經(jīng)成為生物納米材料領(lǐng)域的熱點問題。在本論文中,通過置換反應(yīng)(GRR),制備了一種新型的脂質(zhì)體@金銀合金納米復(fù)合材料,該納米材料表現(xiàn)出從可見到近紅外的表面等離子體共振特性。選取拉曼信號和熒光信號分子的蒽環(huán)類抗惡性腫瘤藥物阿霉素作為目標(biāo)藥物,包載進脂質(zhì)體@金銀合金納米復(fù)合材料,發(fā)現(xiàn)阿霉素藥物分子的拉曼信號由于激光與等離子體的諧振耦合被增強,使其具有表面拉曼增強(SERS)活性,在藥物傳遞過程中,可以通過追蹤拉曼信號檢測藥物傳遞。當(dāng)激光進行輻照,入射光光子激發(fā)金屬納米殼層電子,受激電子向外輻射能量,溫度達到脂質(zhì)體相轉(zhuǎn)變溫度后,內(nèi)容藥物阿霉素釋放,即利用脂質(zhì)體具有相轉(zhuǎn)變溫度及金屬納米殼層的光熱轉(zhuǎn)化效應(yīng),實現(xiàn)藥物的可控釋放。本論文研究的主要內(nèi)容如下:(1)制備脂質(zhì)體@金銀合金納米復(fù)合材料。首先,通過薄膜干燥結(jié)合超聲波分散法制備了尺寸在79 nm的脂質(zhì)體;檸檬酸三鈉(Na3C6H5O7)作為保護劑,通過硼氫化鈉(NaBH4)還原硝酸銀(AgNO3)的方法制備尺寸在4 nm左右的銀納米粒子。隨后,根據(jù)靜電吸引相互作用,在脂質(zhì)體表面包覆并生長一層致密銀殼層。最后,通過銀殼層與氯金酸(HAuCl_4)的氧化還原反應(yīng)(GRR),制備出脂質(zhì)體@金銀合金納米復(fù)合材料。使用掃描、透射電鏡,粒度儀及紫外可見吸收光譜對復(fù)合納米材料進行表征,隨后研究加入金銀體積比例對復(fù)合納米材料的影響并研究了材料的光熱特性,最后通過MTT實驗討論材料毒性,證明材料具有良好的生物相容性。(2)將蒽環(huán)類形抗癌藥物阿霉素(DOX)包載入脂質(zhì)體@金銀合金納米復(fù)合材料,并對復(fù)合材料的表面等離子體共振特性、表面增強拉曼特性以及熒光淬滅特性進行研究。金銀合金納米殼層可以吸收光能通過電磁場共振轉(zhuǎn)移為熱量,而脂質(zhì)體作為一種具有相轉(zhuǎn)變溫度的特殊材料,當(dāng)外界溫度高于相轉(zhuǎn)變溫度時,磷脂分子從膠態(tài)變?yōu)橐簯B(tài),脂質(zhì)體因結(jié)構(gòu)改變而發(fā)生相轉(zhuǎn)變,從而實現(xiàn)內(nèi)容藥物的釋放。當(dāng)用與脂質(zhì)體@金銀合金納米材料表面等離子體共振峰位相匹配波長的激光照射材料時,會實現(xiàn)內(nèi)容藥物阿霉素的釋放。通過光譜吸收強度、MTT實驗、熒光猝滅及恢復(fù)現(xiàn)象,研究并證實了通過光熱觸發(fā)的可控性藥物釋放。
[Abstract]:At present, how to realize the controlled release of drugs and track the drug delivery process has become a hot issue in the field of biomaterials. In this thesis, a new type of liposomes @ gold-silver alloy nanocomposites was prepared by substitution reaction (GRR),. The nanomaterials exhibit surface plasmon resonance (SPR) properties from visible near infrared (NIR). Anthracycline anticancer drug doxorubicin, which is a Raman signal molecule and a fluorescent signal molecule, was selected as the target drug and included in liposomes @ gold and silver alloy nanocomposites. It was found that the Raman signal of doxorubicin molecule was enhanced by the resonance coupling between laser and plasma, which made it have surface Raman enhanced (SERS) activity. In the drug delivery process, the drug transfer could be detected by tracing the Raman signal. When the laser irradiation, the incident photons excite the metal nanoshell electrons, the stimulated electrons radiate the energy outward, and the temperature reaches the phase transition temperature of liposomes, and the content drug doxorubicin is released. That is to say, the controlled release of drugs can be realized by using the phase transition temperature of liposomes and the photothermal conversion effect of metal nanoshells. The main contents of this thesis are as follows: (1) Liposome @ au / Ag alloy nanocomposites were prepared. Firstly, liposomes with size of 79 nm were prepared by thin film drying and ultrasonic dispersion. Trisodium citrate (Na3C6H5O7) was used as protective agent to prepare silver nanoparticles with a size of about 4 nm by reducing silver nitrate (AgNO3) by sodium borohydroxide (NaBH4). Then, according to the electrostatic attraction interaction, a dense silver shell was deposited on the surface of the liposomes. Finally, liposomes @ gold-silver alloy nanocomposites were prepared by redox reaction of silver shell with chlorogold acid (HAuCl_4) (GRR),. The composite nano-materials were characterized by scanning electron microscopy, transmission electron microscopy, particle size analyzer and ultraviolet visible absorption spectrum. Then, the influence of the volume ratio of gold and silver on the composite nano-materials was studied, and the photothermal properties of the composites were also studied. Finally, the toxicity of the material was discussed by MTT test, and it was proved that the material had good biocompatibility. (2) the anthracycline anticancer drug doxorubicin (DOX) was loaded into liposomes @ gold-silver alloy nanocomposites. The surface plasmon resonance properties, surface enhanced Raman properties and fluorescence quenching properties of the composites were studied. Nano-shell of gold-silver alloy can absorb light energy to transfer heat through electromagnetic field resonance, while liposome is a special material with phase transition temperature. When the external temperature is higher than the phase transition temperature, the phospholipid molecule changes from colloid state to liquid state. The phase change of liposomes occurs due to structural changes, so as to realize the release of content drugs. When the laser irradiation wavelength matching the plasmon resonance peak position of liposomes @ gold and silver alloy nanomaterials is used, the release of doxorubicin can be realized. The controllable drug release triggered by photoheat was studied and confirmed by spectral absorption intensity, MTT experiment, fluorescence quenching and recovery.
【學(xué)位授予單位】：東北師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：TB383.1;TB33;TQ460.1

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