基于多功能核—?dú)そY(jié)構(gòu)納米粒子的雙重響應(yīng)藥物控釋與光動(dòng)療研究
發(fā)布時(shí)間：2018-10-21 13:16
【摘要】：傳統(tǒng)的癌癥治療方法有療效低,療程長(zhǎng),成本高,治療風(fēng)險(xiǎn)較大等不利的缺點(diǎn),現(xiàn)今研究工作者專注于開發(fā)新型的癌癥治療手段用以克服這些缺點(diǎn),新型手段中最受關(guān)注的就包括納米粒子靶向給藥技術(shù);已有的研究成果中的納米粒子可以實(shí)現(xiàn)載藥放藥或者光動(dòng)療等技術(shù),而處于研究前沿的新一代載藥納米粒子可以整合載藥、外部響應(yīng)控制放藥、特異性靶向、生物成像、體內(nèi)診斷以及光動(dòng)療等多種作用為一體,制備出多功能新型納米粒子。本文的主要研究?jī)?nèi)容旨在設(shè)計(jì)一種尺寸小于100nm且具有載藥、p H響應(yīng)放藥、光動(dòng)療、特異性靶向及生物成像功能的納米粒子,并著重研究p H刺激響應(yīng)的藥物控釋及光動(dòng)療性能,以實(shí)現(xiàn)在體內(nèi)酸性環(huán)境以及體外近紅外光光照的雙重刺激下達(dá)到藥物控釋和單線態(tài)氧光動(dòng)療的雙重響應(yīng),以實(shí)現(xiàn)雞尾酒療法。在制備方面,本文通過(guò)熱裂解法及溶膠凝膠法,合成并組裝三層核-殼-殼結(jié)構(gòu)的UCNP@SiO_2(MB)@m SiO_2介孔納米粒子,通過(guò)內(nèi)核的鑭系元素離子摻雜上轉(zhuǎn)換納米粒子NaYF_4,Yb~(3+)Er~(3+)的發(fā)射光譜與光敏劑MB的吸收光譜的匹配,在980nm激光激發(fā)下可以產(chǎn)生具有光動(dòng)力治療效果的單線態(tài)氧,并且激發(fā)光具有成像功能;并通過(guò)第三層豐富的介孔結(jié)構(gòu)裝載癌癥治療藥物DOX;合成制備PEI-FA并通過(guò)靜電力作用完成PEI-FA對(duì)載藥粒子的包封;對(duì)三層核-殼-殼結(jié)構(gòu)的UCNP@SiO_2(MB)@m SiO_2的表面進(jìn)行改性修飾,使得通過(guò)PEI-FA包覆的介孔納米粒子載藥量增加。在功能性測(cè)試方面,本文僅對(duì)載藥、p H響應(yīng)控釋效果以及光動(dòng)療方面做了研究性評(píng)估。通過(guò)改性前后的對(duì)比來(lái)說(shuō)明載藥性能的改進(jìn),通過(guò)不同的PEI-FA包封量的核-殼-殼結(jié)構(gòu)納米粒子在不同p H下的藥物釋放曲線來(lái)研究p H刺激響應(yīng)的藥物控釋性能,并通過(guò)測(cè)定DPBF的紫外-可見吸光度的變化曲線來(lái)研究核-殼-殼結(jié)構(gòu)納米粒子的單線態(tài)氧產(chǎn)生能力。最終達(dá)到綜合性評(píng)價(jià)核-殼-殼結(jié)構(gòu)多功能載藥納米粒子UCNP@SiO_2(MB)@m SiO_2性能的結(jié)果以及潛在的生醫(yī)應(yīng)用價(jià)值。
[Abstract]:Traditional cancer treatment methods have the disadvantages of low curative effect, long course of treatment, high cost, high treatment risk and so on. Nowadays, researchers focus on developing new cancer treatment methods to overcome these disadvantages. Among the new methods are the targeted drug delivery technology for nanoparticles, which can be used for drug loading or photodynamic therapy. The new generation of drug loaded nanoparticles, which are in the research frontier, can integrate drug loading, external response control, specific targeting, biological imaging, in vivo diagnosis and photodynamic therapy to produce new multifunctional nanoparticles. The main purpose of this paper is to design a kind of nanoparticles with drug delivery, p H response, photodynamic therapy, specific target and biological imaging function, and to study the drug controlled release and photodynamic therapy performance of p-H stimulation response. In order to achieve the dual response of drug controlled release and single line oxygen phototherapy under the double stimulation of in vivo acidic environment and in vitro near-infrared light irradiation, the cocktail therapy can be realized. In the aspect of preparation, UCNP@SiO_2 (MB) @ m SiO_2 mesoporous nanoparticles with three-layer core-shell structure were synthesized and assembled by pyrolysis and sol-gel method. By matching the emission spectra of NaYF_4,Yb~ (3) Er~ (3) nanoparticles doped with lanthanide ions in the core with the absorption spectra of Guang Min (MB), a single line oxygen with photodynamic effect can be produced under the excitation of 980nm laser. And the excited light has imaging function, and the third layer of rich mesoporous structure is loaded with cancer treatment drug DOX; synthesis to prepare PEI-FA and complete the encapsulation of the drug carrier particles by PEI-FA through electrostatic action. The surface modification of UCNP@SiO_2 (MB) @ m SiO_2 with a three-layer core-shell structure resulted in an increase in the amount of drug loaded by mesoporous nanoparticles coated with PEI-FA. In the aspect of functional test, we only evaluated the controlled release effect of drug loaded, p H and photodynamic therapy. The improvement of drug loading performance was explained by the comparison before and after modification. The drug release properties of p-H stimulated response were studied by the drug release curves of core-shell structure nanoparticles with different PEI-FA entrapment amounts under different pH conditions. The single-line oxygen production ability of core-shell nanoparticles was studied by measuring the UV-Vis absorbance curve of DPBF. Finally, the results of comprehensive evaluation of the properties of core-shell multifunctional drug-loaded nanoparticles UCNP@SiO_2 (MB) @ m SiO_2 and the potential biomedical application value were achieved.
【學(xué)位授予單位】：哈爾濱工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：TB383.1;R943
，
本文編號(hào)：2285197
[Abstract]:Traditional cancer treatment methods have the disadvantages of low curative effect, long course of treatment, high cost, high treatment risk and so on. Nowadays, researchers focus on developing new cancer treatment methods to overcome these disadvantages. Among the new methods are the targeted drug delivery technology for nanoparticles, which can be used for drug loading or photodynamic therapy. The new generation of drug loaded nanoparticles, which are in the research frontier, can integrate drug loading, external response control, specific targeting, biological imaging, in vivo diagnosis and photodynamic therapy to produce new multifunctional nanoparticles. The main purpose of this paper is to design a kind of nanoparticles with drug delivery, p H response, photodynamic therapy, specific target and biological imaging function, and to study the drug controlled release and photodynamic therapy performance of p-H stimulation response. In order to achieve the dual response of drug controlled release and single line oxygen phototherapy under the double stimulation of in vivo acidic environment and in vitro near-infrared light irradiation, the cocktail therapy can be realized. In the aspect of preparation, UCNP@SiO_2 (MB) @ m SiO_2 mesoporous nanoparticles with three-layer core-shell structure were synthesized and assembled by pyrolysis and sol-gel method. By matching the emission spectra of NaYF_4,Yb~ (3) Er~ (3) nanoparticles doped with lanthanide ions in the core with the absorption spectra of Guang Min (MB), a single line oxygen with photodynamic effect can be produced under the excitation of 980nm laser. And the excited light has imaging function, and the third layer of rich mesoporous structure is loaded with cancer treatment drug DOX; synthesis to prepare PEI-FA and complete the encapsulation of the drug carrier particles by PEI-FA through electrostatic action. The surface modification of UCNP@SiO_2 (MB) @ m SiO_2 with a three-layer core-shell structure resulted in an increase in the amount of drug loaded by mesoporous nanoparticles coated with PEI-FA. In the aspect of functional test, we only evaluated the controlled release effect of drug loaded, p H and photodynamic therapy. The improvement of drug loading performance was explained by the comparison before and after modification. The drug release properties of p-H stimulated response were studied by the drug release curves of core-shell structure nanoparticles with different PEI-FA entrapment amounts under different pH conditions. The single-line oxygen production ability of core-shell nanoparticles was studied by measuring the UV-Vis absorbance curve of DPBF. Finally, the results of comprehensive evaluation of the properties of core-shell multifunctional drug-loaded nanoparticles UCNP@SiO_2 (MB) @ m SiO_2 and the potential biomedical application value were achieved.
【學(xué)位授予單位】：哈爾濱工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：TB383.1;R943
，
本文編號(hào)：2285197
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