本文選題：納米銀 + 光熱治療�。� 參考：《中國人民解放軍醫(yī)學(xué)院》2015年博士論文

【摘要】：目的：近幾年,光熱治療(Photothermal therapy,PTT)被廣泛應(yīng)用于腫瘤的治療,然而在眼科的應(yīng)用幾乎是空白。我們研制出一種新型的PTT介質(zhì)——具有二氧化鈦包殼的銀納米粒子(Ag@TiO2 nanoparticles, Ag@ TiO2 NPs),它比其他PTT介質(zhì)具有更加強大的紅外吸收峰以及更強的光熱轉(zhuǎn)換效率卻又成本低廉。本課題通過體內(nèi)體外實驗證實此納米材料可能成為一種新型PTT材料有效的用于皮膚及虹膜黑色素瘤的治療。方法：通過兩步法,在晶種的基礎(chǔ)上合成銀納米粒子。在此基礎(chǔ)上,利用溶膠凝膠法制得具有Ag@ TiO2核殼結(jié)構(gòu)的納米粒子。通過調(diào)節(jié)反應(yīng)時間和溶膠凝膠前驅(qū)體引入量,可以使氧化物殼層的厚度從1-15納米范圍內(nèi)精細(xì)可調(diào)。銀納米粒子的光熱轉(zhuǎn)換效率性質(zhì)通過：用2W·cm-2功率密度的808rnm近紅外光直接照射其在石英池中一毫升不同質(zhì)量分?jǐn)?shù)水溶液來測定。體外實驗用不同濃度的銀納米粒子溶液和B16F10, OCM-1細(xì)胞共培養(yǎng)后,評估銀納米粒子的體外毒性；并通過808nm近紅外激光照射不同濃度的銀納米粒子溶液共培養(yǎng)的細(xì)胞評估銀納米粒子的光熱效果。體內(nèi)實驗構(gòu)造皮下黑色素瘤和前房虹膜膜黑色素瘤動物模型,在局部組織注射一定濃度的銀納米粒子,立刻用近紅外光激光照射。隨后記錄不同時間點實體瘤的體積并評估其體積變化。此外行組織學(xué)檢查鼠尾靜脈注射銀納米粒子老鼠1月后各臟器的變化。結(jié)果：我們開發(fā)出一種簡便的溶膠凝膠法合成Ag@ TiO2納米結(jié)構(gòu),并且實現(xiàn)去厚度可調(diào)。由于氧化物殼層的保護(hù)作用,這種納米粒子在生物體內(nèi)和體外實驗中,均展現(xiàn)出良好的生物相容性和穩(wěn)定性。這種納米粒的局域化的表面等離子共振(plasmon resonance, LSPR)吸收譜帶可調(diào)到近紅外窗口(808納米)。當(dāng)波長為808納米的入射光照射到這種納米粒子表面,其周圍環(huán)境的溫度會明顯隨之升高,直接導(dǎo)致B16F10(p0.01)和OCM-1細(xì)胞(p0.01)死亡。經(jīng)PTT治療后黑色素瘤均變小,皮下腫瘤模型治療16天后瘤體逐漸消失；虹膜黑色素瘤模型治療后三天瘤體體積開始下降。生物毒性實驗提示細(xì)胞對銀納米粒子表現(xiàn)出良好的耐受性，在200μg/ml細(xì)胞仍有較強的活性；同時動物在治療后1個月仍然全部存活。結(jié)論：我們證實Ag@ TiO2是一種局部治療實體腫瘤的有效PTT介質(zhì)。
[Abstract]:Objective: in recent years, photothermic therapy (PTT) has been widely used in the treatment of tumor, but the application of PTT in ophthalmology is almost blank. We have developed a new PTT medium, Ag @ TiO2 NPs (Ag@ TiO2 NPs), which has a stronger infrared absorption peak and higher photothermal conversion efficiency than other PTT media. In vitro and in vivo experiments have proved that this nanometer material may be an effective PTT material for the treatment of skin and iris melanoma. Methods: silver nanoparticles were synthesized on the basis of seed by two-step method. On this basis, nanoparticles with core-shell structure of Ag@ TiO2 were prepared by sol-gel method. By adjusting the reaction time and the amount of sol-gel precursor, the thickness of oxide shell can be adjusted from 1-15 nm to 15 nm. The photothermal conversion efficiency properties of silver nanoparticles were measured by direct irradiation of 808rnm near infrared light with 2W cm-2 power density in quartz cell with different mass fraction aqueous solution. The in vitro toxicity of silver nanoparticles was evaluated by co-culture of B16F10 and OCM-1 cells with different concentrations of silver nanoparticles. The photothermal effect of silver nanoparticles was evaluated by 808nm near infrared laser irradiation of silver nanoparticles co-cultured in different concentrations. The animal models of subcutaneous melanoma and anterior chamber iris melanoma were constructed in vivo. A certain concentration of silver nanoparticles was injected into local tissues and immediately irradiated with near-infrared laser. The volume of solid tumor was then recorded and evaluated at different time points. In addition, the changes of organs were examined by histological examination after injecting silver nanoparticles into tail vein of mice for one month. Results: we developed a simple sol-gel method for the synthesis of Ag@ TiO2 nanostructures, and the thickness of Ag@ TiO2 nanostructures was adjustable. Because of the protective effect of oxide shell, the nanoparticles showed good biocompatibility and stability in vivo and in vitro. The localized surface plasmon resonance (plasmon resonance,) absorption band of the nanoparticles can be adjusted to the near infrared window (808 nm). When the incident light at the wavelength of 808 nm irradiates on the surface of the nanoparticles, the ambient temperature will increase obviously, which will lead to the death of B16F10 (p0.01) and OCM-1 cells (p0.01). After PTT treatment, melanoma became smaller, subcutaneous tumor model gradually disappeared 16 days after treatment, and the volume of tumor began to decrease three days after the treatment of iris melanoma model. The biotoxicity test showed that the cells showed good tolerance to silver nanoparticles, and still had strong activity in 200 渭 g/ml cells, and all the animals survived one month after treatment. Conclusion: we confirm that Ag@ TiO2 is an effective PTT medium for local treatment of solid tumors.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R739.5;R739.7

【相似文獻(xiàn)】

相關(guān)期刊論文 前7條

1 蘇小東;賈云;李毅;;銀納米粒子探針等離子共振散射光譜法測定抗壞血酸[J];應(yīng)用化學(xué);2010年12期

2 趙亞利;楊濤;張英;高紅云;席亞楠;;溶菌酶穩(wěn)定的銀納米粒子的合成及穩(wěn)定性研究[J];醫(yī)學(xué)研究與教育;2014年04期

3 呂曉迎;黃炎;馬靖武;;基于生物組學(xué)方法的銀納米粒子細(xì)胞毒性機理研究[J];口腔材料器械雜志;2010年04期

4 李靖云;王q，

本文編號：2111430