本文選題：多巰基磺酸甜菜堿 + 金納米桿��； 參考：《浙江大學(xué)》2014年碩士論文

【摘要】：目的：納米顆粒的低毒性是其在生物利用的先決條件。我們?cè)噲D開(kāi)發(fā)一種帶新型修飾配體即多巰基磺酸甜菜堿聚合物(簡(jiǎn)稱PTSB)的金納米桿,評(píng)價(jià)該P(yáng)TSB-金納米桿在小鼠體內(nèi)的組織分布和急性毒性作用,進(jìn)一步探討該P(yáng)TSB-金納米桿在紅外熱療輔助下對(duì)裸鼠鼻咽癌移植瘤的治療作用,從而尋找治療鼻咽癌的一種新方法。 材料和方法：兩性離子磺酸甜菜堿(sB)形成聚合物通過(guò)多個(gè)巰基與金納米桿牢固結(jié)合,構(gòu)建PTSB-金納米桿。以ICR小鼠為對(duì)象,按最大給藥劑量經(jīng)尾靜脈注射給藥,在4小時(shí)、24小時(shí)和48小時(shí)三個(gè)時(shí)間點(diǎn)觀察小鼠體重、血液學(xué)及肝腎功能,電感耦合等離子體質(zhì)譜(ICP-MS)檢測(cè)小鼠血液和主要臟器的金納米桿含量,組織病理學(xué)分析金納米桿對(duì)臟器是否損傷,透射電鏡確認(rèn)金納米桿是否進(jìn)入組織細(xì)胞內(nèi)。以BALB/C裸鼠為對(duì)象,不同濃度金納米桿、兩種給藥途徑和不同近紅外線照射時(shí)間作為實(shí)驗(yàn)處理因素,觀察裸鼠鼻咽癌移植瘤的體積變化、腫瘤增殖率、瘤體病理學(xué)及透射電鏡表現(xiàn)。 結(jié)果：本實(shí)驗(yàn)構(gòu)建的PTSB-金納米桿在近紅外區(qū)有很強(qiáng)烈的光吸收作用,在生理?xiàng)l件下具有很好的穩(wěn)定性和生物相容性。靜脈給藥后,ICR小鼠一般狀況良好,體重、血液學(xué)及肝腎功能與對(duì)照組相比無(wú)明顯異常,ICP-MS檢測(cè)發(fā)現(xiàn)金納米桿可經(jīng)血液循環(huán)到達(dá)各重要臟器,且肝和脾是其主要蓄積器官,臟器病理學(xué)顯示無(wú)明顯損傷,透射電鏡確認(rèn)金納米桿進(jìn)入肝、脾和腎細(xì)胞內(nèi),且大多數(shù)出現(xiàn)在溶酶體,少數(shù)在細(xì)胞質(zhì)、線粒體。裸鼠鼻咽癌抑瘤實(shí)驗(yàn)顯示,治療組瘤體縮小,表面皺縮,隨著金納米桿瘤內(nèi)給藥濃度的增加,近紅外線照射時(shí)間的增長(zhǎng),治療組的相對(duì)腫瘤增殖率呈下降趨勢(shì),腫瘤抑制率呈上升趨勢(shì)。瘤內(nèi)給藥組與靜脈注射給藥組相比,同一給藥濃度下,瘤內(nèi)組療效稍差于靜脈組。換算成同一給藥劑量下,瘤內(nèi)組的療效優(yōu)于靜脈組。照射1.5h和4h療效優(yōu)于照射0.5h,但1.5h和4h之間對(duì)腫瘤抑制率的影響差別不顯著。瘤體病理學(xué)顯示治療組腫瘤細(xì)胞不同程度變性壞死,腫瘤血管發(fā)育差,淋巴細(xì)胞浸潤(rùn)程度減輕。透射電鏡顯示金納米桿進(jìn)入腫瘤組織,較多的分布在細(xì)胞內(nèi)的溶酶體,部分散在于細(xì)胞質(zhì),腫瘤細(xì)胞可見(jiàn)凋亡。 結(jié)論：PTSB-金納米桿合成過(guò)程簡(jiǎn)便,具有很好的穩(wěn)定性和生物相容性,是應(yīng)用于腫瘤紅外熱療有前景的納米材料。PTSB-金納米桿按最大劑量給藥后可隨血液循環(huán)到達(dá)各重要臟器,主要蓄積在肝和脾,對(duì)小鼠一般狀況和臟器不產(chǎn)生毒性作用,認(rèn)為可安全地應(yīng)用于抑瘤實(shí)驗(yàn)。PTSB-金納米桿在紅外熱療輔助下對(duì)裸鼠鼻咽癌移植瘤有抑制作用,同一給藥劑量下,瘤內(nèi)組的療效優(yōu)于靜脈組。本實(shí)驗(yàn)有望為治療鼻咽癌提供一種可能的新的治療方法。
[Abstract]:Objective: low toxicity of nanoparticles is a prerequisite for bioutilization. We attempted to develop a gold nanorods with a novel modified ligand, polymercaptosulfonic betaine polymer (PTSBs), to evaluate the tissue distribution and acute toxicity of PTSB-gold nanorods in mice. To explore the therapeutic effect of PTSB-gold nanorods in nude mice with nasopharyngeal carcinoma (NPC) transplantation assisted by infrared hyperthermia, and to find a new method for the treatment of nasopharyngeal carcinoma (NPC). Materials and methods: PTSB-gold nanorods were constructed by solid combination of sulfhydryl groups and gold nanorods formed by amphoteric ion betaine sulfonic acid (betaine) B). ICR mice were treated by tail vein injection according to the maximum dose. The body weight, hematology, liver and kidney function were observed at four hours, 24 hours and 48 hours, respectively. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the content of gold nanorods in blood and main organs of mice. Histopathology was used to analyze whether gold nanorods were damaged or not, and transmission electron microscopy (TEM) was used to confirm whether gold nanorods entered the tissues and cells. BALB/C nude mice with different concentrations of gold nanorods, two ways of administration and different time of near-infrared irradiation were used as experimental factors to observe the volume change and tumor proliferation rate of nasopharyngeal carcinoma xenografts in nude mice. Pathological and transmission electron microscopic findings of the tumor. Results: PTSB-gold nanorods have strong photoabsorption in near infrared region and good stability and biocompatibility under physiological conditions. After intravenous administration, ICR mice were generally in good condition. There was no obvious abnormality in body weight, hematology, liver and kidney function. ICP-MS was used to detect that the hair cash nanorods could reach all important organs through blood circulation, and liver and spleen were the main accumulative organs of ICR mice. The pathology of viscera showed no obvious damage. Transmission electron microscope confirmed that gold nanorods entered into liver spleen and kidney cells and most of them appeared in lysosomes a few in cytoplasm and mitochondria. The tumor inhibition test in nude mice showed that the tumor body in the treatment group was smaller and the surface shrank. With the increase of the concentration of gold nanorods and the increase of the time of near-infrared irradiation, the relative tumor proliferation rate of the treatment group showed a decreasing trend. The tumor inhibition rate was on the rise. Compared with intravenous administration group, the effect of intratumor group was slightly worse than that of intravenous group under the same administration concentration. The curative effect of intratumoral group was better than that of intravenous group under the same dosage. The effect of 1.5 h and 4 h irradiation was better than that of 0.5 h irradiation, but there was no significant difference between 1.5 h and 4 h on tumor inhibition rate. Tumor pathology showed that the tumor cells in the treatment group were denatured and necrotic to varying degrees, the tumor vascular development was poor, and the degree of lymphocytic infiltration was reduced. Transmission electron microscopy (TEM) showed that gold nanorods entered the tumor tissue, and the lysosomes were distributed in the cells, some of which were scattered in the cytoplasm, and apoptosis was observed in the tumor cells. Conclusion the synthesis process of the gold nanorods is simple and has good stability and biocompatibility. It is a promising nanomaterial for tumor infrared hyperthermia. PTSB-gold nanorods can reach various important organs with blood circulation at the maximum dose. It is considered that PTSB-gold nanorods can be safely used in tumor inhibition experiment. PTSB-gold nanorods can inhibit the transplanted tumor of nasopharyngeal carcinoma in nude mice assisted by infrared hyperthermia. The curative effect of intratumoral group was better than that of venous group. This study is expected to provide a new treatment for nasopharyngeal carcinoma.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R739.63

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