本文選題：p　切入點(diǎn)：H響應(yīng)性　出處：《河北北方學(xué)院》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：核殼式磁性介孔硅納米復(fù)合物是以磁性納米粒為核,介孔硅材料為殼而形成的納米復(fù)合材料。它不僅具備了磁性納米粒及介孔硅材料各自所具有的特性如磁靶向性、高的比表面積、易于修飾的內(nèi)表面等,而且還克服了磁性納米容易團(tuán)聚、氧化的缺點(diǎn),使其在生物醫(yī)藥、環(huán)境、化工等研究領(lǐng)域有著良好的應(yīng)用。光動(dòng)力療法(Photodynamic Therapy,PDT)是一種新型腫瘤治療方法,主要利用光敏劑在特定波長(zhǎng)光的作用下,產(chǎn)生單線態(tài)氧,對(duì)腫瘤細(xì)胞進(jìn)行殺傷,達(dá)到腫瘤治療目的。光動(dòng)力療法在治療黑素瘤、乳腺癌等表淺性腫瘤方面有很好的應(yīng)用,同時(shí)在治療HPV病毒感染如內(nèi)、外陰陰道尖銳濕疣等方面也有重要作用,目前光敏劑已成為新型抗腫瘤藥物研究的熱點(diǎn)之一。但PDT目前仍存在一些問(wèn)題,主要是患者在治療過(guò)程中需要全程避光,否則會(huì)產(chǎn)生嚴(yán)重的全身性光毒副作用,使用非常不便;另一方面,光敏劑的體內(nèi)分布缺少明確的腫瘤靶向,腫瘤部位有效濃度不高,影響光動(dòng)力治療的效果并導(dǎo)致毒副作用的產(chǎn)生。本課題針對(duì)光動(dòng)力治療中的該主要問(wèn)題,采用現(xiàn)代納米技術(shù)構(gòu)建出能夠把光敏劑有效靶向腫瘤部位的響應(yīng)性納米載藥系統(tǒng),達(dá)到光敏劑有效靶向腫瘤部位,并在腫瘤局部響應(yīng)釋放,以有效提高腫瘤組織藥物濃度,降低全身毒副作用。首先我們?cè)O(shè)計(jì)合成了核殼式磁性Fe3O4介孔硅納米復(fù)合物(MMSN),利用其負(fù)載光敏劑孟加拉紅(RB),并在介孔硅表面功能性的修飾具有pH響應(yīng)的嵌段聚合物聚乙二醇-b-聚天冬氨酸(PEG-b-PAsp),形成pH響應(yīng)核殼式磁性介孔硅納米復(fù)合物(RB-MMSNs),并對(duì)其進(jìn)行了相關(guān)表征。通過(guò)透射電鏡觀察合成的MMSN的微觀形態(tài),其納米粒徑在190nm左右,具有規(guī)則的球狀形貌且介孔特性良好。通過(guò)在介孔硅表面修飾PEG-b-PAsp使RB-MMSNs具有一定的pH響應(yīng)性,并在實(shí)驗(yàn)過(guò)程中發(fā)現(xiàn)其也可以增加介孔硅層對(duì)RB的載藥,使得RB負(fù)載率高達(dá)36%左右。體外測(cè)得RB-MMSNs的磁飽和強(qiáng)度約達(dá)26.6emu/g,弛豫率接近52.52S-1mM-1,具有較好的磁靶向作用,并有可能用于磁共振成像。其次通過(guò)體外細(xì)胞實(shí)驗(yàn)考察了RB-MMSNs的體外磁靶向性及光動(dòng)力效果。CCK-8的檢測(cè)結(jié)果可知RB-MMSNs無(wú)顯著的暗毒性,相較于游離的RB,該材料能很好的被小鼠黑色素瘤B16細(xì)胞攝取,且在施加外部磁場(chǎng)部位的納米復(fù)合物細(xì)胞攝取量顯著增加。經(jīng)LED綠光燈照射,RB-MMSNs對(duì)B16細(xì)胞的半數(shù)抑制濃度為4.85μg/mL,而游離RB高達(dá)48.86μg/mL。CCK-8及流式凋亡細(xì)胞檢測(cè)結(jié)果均顯示RB-MMSNs對(duì)B16細(xì)胞殺傷能力高于同濃度的游離RB10倍左右,因此RB-MMSNs能極大程度的提高體外光動(dòng)力殺傷B16細(xì)胞的效率。最后通過(guò)體內(nèi)動(dòng)物實(shí)驗(yàn)進(jìn)一步研究了RB-MMSNs對(duì)小鼠B16黑色素移植瘤的PDT效果。小鼠磁共振成像(MRI)及普魯士染色實(shí)驗(yàn)結(jié)果均表明RB-MMSNs在外磁場(chǎng)作用下具有體內(nèi)腫瘤靶向性。動(dòng)物實(shí)驗(yàn)結(jié)果顯示,在施加了磁場(chǎng)并結(jié)合光療的實(shí)驗(yàn)小鼠組中,腫瘤體積最小,并具有統(tǒng)計(jì)學(xué)差異,同時(shí)該組小鼠的生存期相對(duì)最長(zhǎng),TUNEL凋亡檢測(cè)結(jié)果也輔助證明了這一點(diǎn),表明RB-MMSNs具有良好的體內(nèi)腫瘤治療效果�？傊�,我們構(gòu)建合成的RB-MMSNs納米復(fù)合物具有較高的光敏劑負(fù)載率,明顯的體內(nèi)外磁靶向性和pH響應(yīng)釋放特性,以及低的毒副作用,很大程度的解決了絕大多數(shù)光敏劑在腫瘤組織部位有效濃度不高,體內(nèi)運(yùn)輸過(guò)程中易泄露而導(dǎo)致毒副作用大等問(wèn)題,有望成為一種集磁靶向性、pH響應(yīng)性于一身的多功能納米載體,增強(qiáng)光動(dòng)力治療腫瘤的效果。
[Abstract]:Core-shell magnetic mesoporous silica nanocomposite with magnetic nanoparticles as core and nano composite mesoporous silica shell formed. It not only has the magnetic nanoparticles and mesoporous silica materials with their properties such as magnetic targeting, high specific surface area, easy modification of the inner surface, but also overcome the magnetic nanoparticles are easy to agglomerate, oxidation defects, the environment in the field of chemical, biological medicine, and so on. It has a good application of photodynamic therapy (Photodynamic Therapy PDT) is a new method for tumor therapy, mainly using photosensitizer in the light of a specific wavelength under the action of singlet oxygen the tumor cell killing, achieve tumor therapy. Photodynamic therapy in the treatment of melanoma, a very good application of breast cancer and other superficial tumor, at the same time in the treatment of HPV infection, such as, vulvovaginal condyloma acuminatum has The important role the photosensitizer has become one of the hot research of new anti-tumor drug. But the PDT still has some problems, mainly the whole patients need light in the treatment process, or will cause severe systemic side effects of light, use very inconvenient; on the other hand, the lack of photosensitizer distribution in vivo tumor target clear to the tumor site, effective concentration is not high, influence the effect of photodynamic treatment and lead to the emergence of side effects. Aiming at the main problems in photodynamic therapy, can construct the light sensitive agent effective targeting of tumor response nano drug carrier system by modern nanotechnology, to achieve effective targeting photosensitizer the tumor site, and in response to the release of local tumor, improve the drug concentration of tumor tissue and reduce systemic side effects. First we design a core-shell Fe3O4 magnetic mesoporous silica nanoparticles synthesized Compound (MMSN), using the load of photosensitizer Rose Bengal (RB), and pH response of block copolymer polyethylene glycol -b- polyaspartic acid on modified functional mesoporous silicon surface (PEG-b-PAsp), the formation of pH response core-shell mesoporous silica nanocomposite (RB-MMSNs), and the the characterization of morphology observed by transmission electron microscopy. The synthesis of MMSN, the nano particle size of about 190nm, with regular spherical morphology and mesoporous characteristics are good. Through surface modification of mesoporous silica PEG-b-PAsp RB-MMSNs has a pH response, and in the course of the experiment found that it can also increase the mesoporous silicon layer the RB loading, the RB load rate as high as 36%. RB-MMSNs test in vitro magnetic saturation intensity of about 26.6emu/g, the relaxation rate is close to 52.52S-1mM-1, has good effect to the magnetic target, and may be used in magnetic resonance imaging. Followed by fine in vitro 鑳?yōu)瀹為獙瑁?

本文編號(hào)：1569024