本文關(guān)鍵詞：阿霉素磁靶向光敏脂質(zhì)體的制備及其在腫瘤光熱—化療聯(lián)合治療中的應(yīng)用　出處：《江蘇大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： Fe_3O_4 熱敏脂質(zhì)體 觸發(fā)釋放 光熱治療 聯(lián)合治療 成像

【摘要】：脂質(zhì)體作為一種常見(jiàn)的藥物載體,能夠有效地增強(qiáng)藥物的穩(wěn)定性,降低毒副作用。然而,常規(guī)的脂質(zhì)體往往不能實(shí)現(xiàn)藥物在病理部位的定點(diǎn)和定位釋放。光熱治療(Photothermal therapy,PTT)是一種新型的治療手段,在腫瘤的治療方面具有良好的應(yīng)用前景。Fe_3O_4納米粒具有低毒性、超順磁性以及良好的光熱轉(zhuǎn)換特性,可以作為一種理想的光敏劑應(yīng)用于腫瘤的光熱治療。在本研究中,我們基于Fe_3O_4納米粒和熱敏脂質(zhì)體(thermosensitive liposomes,TSL),構(gòu)建了一種兼具了磁靶向、光熱以及熱敏釋放等特性的多功能藥物載體,又稱為磁靶向光敏脂質(zhì)體(Fe_3O_4-TSL)。選用阿霉素(Doxorubicin,DOX)作為模板藥物,通過(guò)硫酸銨梯度法進(jìn)行了藥物的負(fù)載,構(gòu)建了阿霉素磁靶向光敏脂質(zhì)體(DOXFe_3O_4-TSL),并將其應(yīng)用于體內(nèi)外光熱-化療協(xié)同治療腫瘤的研究。具體內(nèi)容如下:一、分別采用高溫?zé)岱纸夥ê湍嫦蛘舭l(fā)法制備了油溶性的Fe_3O_4磁性納米粒和Fe_3O_4-TSL藥物載體,并對(duì)其進(jìn)行了表征。結(jié)果顯示所制得的Fe_3O_4納米粒,具有近紅外吸收特性并表現(xiàn)出超順磁性和磁性。該納米粒被包裹在脂質(zhì)雙分子層中,其負(fù)載會(huì)使得脂質(zhì)體的粒徑有所增大,但是不會(huì)對(duì)其相變溫度產(chǎn)生影響。此外,該Fe_3O_4-TSL表現(xiàn)出良好的體外磁共振響應(yīng)性和近紅外(near-infrared,NIR)光熱升溫效果。選擇MCF-7細(xì)胞為模型,考察了Fe_3O_4-TSL的細(xì)胞毒性,結(jié)果表明Fe_3O_4-TSL毒性較低、生物相容性較好。二、采用硫酸銨梯度法對(duì)TSL及Fe_3O_4-TSL進(jìn)行了DOX的負(fù)載。通過(guò)比較DOXFe_3O_4-TSL與DOX-TSL的NIR光控釋放效果,結(jié)果表明Fe_3O_4的負(fù)載使得脂質(zhì)體中的DOX可通過(guò)NIR光觸發(fā)釋放。細(xì)胞實(shí)驗(yàn)結(jié)果表明DOXFe_3O_4-TSL可以被腫瘤細(xì)胞攝取,在NIR激光觸發(fā)下,DOX從DOXFe_3O_4-TSL中釋放出來(lái)并進(jìn)入細(xì)胞核。對(duì)DOXFe_3O_4-TSL的體外抗腫瘤效果進(jìn)行評(píng)價(jià),結(jié)果發(fā)現(xiàn)單純的光熱治療抗腫瘤效果有限,而光熱治療結(jié)合化療則能大大增強(qiáng)腫瘤的治療效果。三、構(gòu)建S180荷瘤小鼠模型,研究了DOXFe_3O_4-TSL的體內(nèi)腫瘤靶向性及抗腫瘤效果。尾靜脈注射后,Fe_3O_4-TSL能夠逐漸靶向聚集于腫瘤部位,并表現(xiàn)出良好的體內(nèi)磁共振成像效果和光熱效應(yīng)。體內(nèi)抗腫瘤結(jié)果顯示,DOXFe_3O_4-TSL的光熱-化療抗腫瘤效果明顯優(yōu)于單純的光熱治療或化療,且組織病理學(xué)檢查表明其在治療過(guò)程中并沒(méi)有對(duì)正常組織造成損傷。
[Abstract]:Liposomes as a drug carrier common, can effectively enhance the stability of drugs, reduce side effects. However, conventional liposomes often cannot achieve drug release in point and positioning. Pathology of photothermal therapy (Photothermal therapy PTT) is a new type of treatment, it has a good application prospect.Fe_3O_4 nanoparticles in the treatment of tumors with low toxicity, superparamagnetism and good thermal properties, thermal treatment can be used as a kind of ideal photosensitizer used in tumor. In this study, we based on nanoparticles and thermal Fe_3O_4 of liposome (thermosensitive liposomes, TSL), constructed a with magnetic targeting multifunctional drug carrier, and the thermal characteristics of photothermal release, also known as magnetic targeting photosensitive liposomes (Fe_3O_4-TSL) with adriamycin (Doxorubicin, DOX) as a template by drugs The ammonium sulfate gradient method for drug loading, constructed adriamycin magnetic targeting photosensitive liposomes (DOXFe_3O_4-TSL), and study its application in vivo photothermal chemotherapy synergistic. The specific contents are as follows: first, using high temperature oil soluble Fe_3O_4 magnetic nanoparticles and Fe_3O_4-TSL of the prepared drug carrier and method reverse evaporation method for decomposition and characterized. The results showed that the prepared Fe_3O_4 nanoparticles with near infrared absorption properties and show superparamagnetic and magnetic nanoparticles. It was wrapped in the lipid bilayer, the load will make the liposome size increased, but it does not influence the phase transition temperature. In addition, the Fe_3O_4-TSL showed good in vitro magnetic resonance response and near infrared (near-infrared, NIR). Select the MCF-7 photothermal heating effect cells as a model, effects of cytotoxic Fe_3O_4-TSL And the results show that Fe_3O_4-TSL has low toxicity, good biocompatibility. Two, the load on the DOX on TSL and Fe_3O_4-TSL were studied by means of ammonium sulfate gradient method. The effect of release by NIR light control comparison of DOXFe_3O_4-TSL and DOX-TSL, the results show that the Fe_3O_4 load makes the liposomes DOX by NIR light triggered release. The experimental results show that the cell DOXFe_3O_4-TSL can be cancer cells in NIR laser triggered, DOX released from DOXFe_3O_4-TSL and enter the nucleus. Evaluation of antitumor effect of DOXFe_3O_4-TSL in vitro, the results found that light heat treatment of the simple anti-tumor effect is limited, and photothermal therapy combined with chemotherapy can greatly enhance the effect of tumor therapy. Three, the construction of S180 bearing mice were studied in vivo tumor targeting of DOXFe_3O_4-TSL and anti tumor effect. After intravenous injection, Fe_3O_4-TSL can gradually gathered in the target The tumor site, and demonstrated in vivo magnetic resonance imaging and photothermal effect. Good antitumor results showed antitumor effect was better than photothermal therapy or chemotherapy DOXFe_3O_4-TSL photothermal chemotherapy, and histopathological examination showed that the treatment process does not cause damage to normal tissue.

【學(xué)位授予單位】：江蘇大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R943;R96

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本文編號(hào)：1406050