本文選題：腫瘤骨轉(zhuǎn)移 + 介孔二氧化硅納米顆粒��； 參考：《河北大學(xué)》2017年碩士論文

【摘要】：腫瘤骨轉(zhuǎn)移一旦發(fā)生,癌癥患者的生存幾率與生活質(zhì)量都將大大降低。隨著納米技術(shù)的迅猛發(fā)展,納米材料由于其納米尺度所固有的獨(dú)特物理性質(zhì),在腫瘤治療方面發(fā)揮著重要的作用,其可以通過EPR效應(yīng)被動(dòng)選擇腫瘤細(xì)胞進(jìn)行治療。然而,由于轉(zhuǎn)移病灶并未形成血管漏洞,所以EPR效應(yīng)并不能應(yīng)用于腫瘤骨轉(zhuǎn)移,如何靶向轉(zhuǎn)移病灶尤其是骨轉(zhuǎn)移病灶依舊迫切需要解決。目前臨床當(dāng)中采用化療藥與雙磷酸鹽聯(lián)合給藥的模式進(jìn)行腫瘤骨轉(zhuǎn)移的治療,但傳統(tǒng)的治療技術(shù)很難達(dá)到理想效果,受限于化療藥物和雙磷酸鹽很難同時(shí)到達(dá)腫瘤部位,協(xié)同發(fā)揮作用。本課題設(shè)計(jì)并構(gòu)建了一種新型的基于介孔二氧化硅納米顆粒(MSNs)的腫瘤化療-雙磷酸鹽/熱療-雙磷酸鹽聯(lián)合治療靶向遞釋系統(tǒng)。該系統(tǒng)利用MSNs孔道高效負(fù)載藥物或包覆納米金棒實(shí)現(xiàn)近紅外光熱轉(zhuǎn)換,并通過修飾雙磷酸鹽主動(dòng)靶向骨及骨的微環(huán)境。本文第一部分為DOX@MSNs-ZOL的構(gòu)建、表征和腫瘤骨轉(zhuǎn)移的治療評價(jià)。合成了粒徑為40 nm的單分散介孔二氧化硅納米顆粒,表面修飾ZOL后負(fù)載抗腫瘤藥DOX,構(gòu)建了一種可以靶向骨的可控釋藥體系。由于合適的介孔孔道和巨大的比表面積,MSNs-ZOL在pH=7.4的PBS溶液中負(fù)載DOX藥量為77.34%。DOX釋放為pH依賴型,在酸性環(huán)境中釋放較快,通過能量依賴介導(dǎo)的方式進(jìn)入細(xì)胞后定位到細(xì)胞溶酶體,并且對腫瘤細(xì)胞有明顯的協(xié)同治療作用,能有效抑制腫瘤轉(zhuǎn)移。第二部分為采用晶種法合成均一的金納米棒(Au),然后利用Au表面的CTAB作為模板劑,加入TEOS形成MSNs包覆Au的核殼結(jié)構(gòu),有兩個(gè)SPR峰,橫向SPR峰為530 nm,縱向SPR峰為808 nm。納米顆粒比表面積為176.06 m2/g,平均孔道直徑2.4 nm。同樣在納米顆粒表面進(jìn)行了ZOL的修飾。Au@MSNs-ZOL可吸收近紅外激光并將其轉(zhuǎn)換成大量的熱能,發(fā)熱效率與納米粒的濃度、激光照射強(qiáng)度、激光照射時(shí)間相關(guān)。Au@MSNs-ZOL的細(xì)胞攝取和腫瘤靶向特性考察,共聚焦熒光顯微鏡和流式細(xì)胞儀直觀結(jié)果顯示MDA-MB-231細(xì)胞對Au@MSNs-ZOL的孵育時(shí)間越長,細(xì)胞攝取越多。體內(nèi)及體外實(shí)驗(yàn)證明,該體系對腫瘤細(xì)胞有明顯的協(xié)同治療作用,能有效抑制腫瘤轉(zhuǎn)移,且具有良好的光聲成像作用,可用于體內(nèi)監(jiān)測。
[Abstract]:Once tumor bone metastases occur, the survival rate and quality of life of cancer patients will be greatly reduced. With the rapid development of nanotechnology, nanomaterials play an important role in tumor therapy because of their unique physical properties in nanometer scale. They can be used to treat tumor cells passively through EPR effect. However, due to the absence of vascular loopholes in metastatic lesions, the EPR effect cannot be applied to tumor bone metastasis. How to target metastatic lesions, especially bone metastases, still needs to be solved urgently. At present, chemotherapy drugs combined with bisphosphates are used to treat tumor bone metastases in clinical practice. However, the traditional treatment techniques are difficult to achieve the desired results, which are limited by the difficulty of both chemotherapy drugs and bisphosphates reaching the tumor site at the same time. Play a synergistic role. A novel tumor chemotherapy-bisphosphate / hyperthermal-bisphosphate targeted delivery system based on mesoporous silica nanoparticles was designed and constructed. The system uses MSNs channels to efficiently load drugs or coated nanocrystalline gold rods to achieve near infrared photothermal conversion and by modifying bisphosphates to actively target bone and bone microenvironment. The first part of this paper is the construction, characterization of DOX@MSNs-ZOL and evaluation of the treatment of tumor bone metastasis. The monodisperse mesoporous silica nanoparticles with the diameter of 40 nm were synthesized and the antitumor drug DOX was loaded on the surface modified by ZOL. A controlled release drug system was constructed which could target the bone. Due to the suitable mesoporous channels and large specific surface area of MSNs-ZOL in PBS solution of pH=7.4, the amount of DOX loaded with 77.34%.DOX was released as a pH dependent type, and released rapidly in acidic environment. The lysosomes of the cells were located after entering the cells in an energy-dependent manner. And has the obvious synergistic effect to the tumor cell, can suppress the tumor metastasis effectively. In the second part, the uniform au nanorods were synthesized by the method of crystal seeding, and then TEOS was added to the au surface as template to form the core-shell structure of au coated with MSNs. There were two SPR peaks, the transverse SPR peak was 530nm, and the longitudinal SPR peak was 808 nm. The specific surface area of nanoparticles is 176.06 m2 / g, and the average pore diameter is 2.4 nm. The surface of nanoparticles was also modified by ZOL. Aur MSNs-ZOL absorbed near infrared laser and converted it into a large amount of heat energy. The heating efficiency, the concentration of nanoparticles, the intensity of laser irradiation, The cell uptake and tumor targeting characteristics of MSNs-ZOL were investigated. The results of confocal fluorescence microscopy and flow cytometry showed that the longer the incubation time of Au@MSNs-ZOL was, the more the cell uptake was. Experiments in vivo and in vitro show that the system has obvious synergistic effect on tumor cells, can effectively inhibit tumor metastasis, and has a good photoacoustic imaging effect, which can be used for in vivo monitoring.
【學(xué)位授予單位】：河北大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R943;TB383.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 Kenneth C.Valkenburg;Matthew R.Steensma;Bart O.Williams;Zhendong Zhong;;Skeletal metastasis:treatments,mouse models,and the Wnt signaling[J];Chinese Journal of Cancer;2013年07期

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本文編號：1893807