本文選題：近紅外染料 + IR780��； 參考：《南京大學(xué)》2016年博士論文

【摘要】：本研究中我們利用小鼠原位腎腫瘤模型探索了PEG-IR780-C13及NIR激光用于熱消融腎腫瘤的可行性。另外,我們還評(píng)估了PEG-IR780-C13及NIR激光熱消融腎腫瘤時(shí)對(duì)于正常腎組織的影響。體外實(shí)驗(yàn)結(jié)果表明,RENCA細(xì)胞主要通過(guò)小窩介導(dǎo)的內(nèi)吞作用攝取PEG-IR780-C13膠束。PEG-IR780-C13被RENCA細(xì)胞攝取之后主要分布于細(xì)胞的溶酶體及晚期內(nèi)涵體中。在NIR激光的照射下,PEG-IR780-C13能夠高效地將光能轉(zhuǎn)化為熱能,用于殺傷RENCA細(xì)胞以及小鼠原位腎腫瘤。同時(shí)我們發(fā)現(xiàn)PEG-IR780-C13膠束及NIR激光熱消融腎腫瘤同時(shí)也會(huì)導(dǎo)致腎腫瘤周圍小部分正常腎組織的損傷,但這一損傷非常局限,并未導(dǎo)致小鼠腎功能的損害。我們的實(shí)驗(yàn)結(jié)果表明,PEG-IR780-C13及NIR激光介導(dǎo)的光熱效應(yīng)能夠產(chǎn)生腫瘤特異性的熱能殺傷腫瘤組織。這一方法為臨床提供了一種更加微創(chuàng)的熱消融腎腫瘤的方法。全氟化碳制劑的放療增敏作用曾被廣泛研究,但是放療前或放療時(shí)需要額外供氧限制了其使用。本研究合成全氟己烷脂質(zhì)體用于腎癌放療增敏。尾靜脈注射全氟己烷脂質(zhì)體后,我們通過(guò)B超及小動(dòng)物成像發(fā)現(xiàn),全氟己烷脂質(zhì)體注射24小時(shí)后在瘤內(nèi)大量聚集。所以,我們?cè)谧⑸淙和橹|(zhì)體24小時(shí)后常氧下對(duì)小鼠皮下移植瘤進(jìn)行X射線照射。實(shí)驗(yàn)小鼠隨機(jī)分為四組：生理鹽水組、脂質(zhì)體組、X線組、脂質(zhì)體+X線組。我們通過(guò)腫瘤體積和腫瘤組織學(xué)來(lái)評(píng)估脂質(zhì)體放療增敏的效果及安全性。結(jié)果顯示,脂質(zhì)體+X線組小鼠腫瘤生長(zhǎng)明顯比單獨(dú)X線組延緩,組織染色顯示脂質(zhì)體+X線組小鼠腫瘤凋亡明顯強(qiáng)于單獨(dú)X線組。另外,全氟己烷脂質(zhì)體對(duì)其他重要臟器組織沒(méi)有明顯副損傷�？傊�,全氟己烷脂質(zhì)體能有效聚集于腫瘤部位并在常氧下增加腎癌放療敏感性。
[Abstract]:In this study, we investigated the feasibility of thermal ablation of renal tumors by PEG-IR780-C13 and NIR laser using in situ renal tumor model in mice. In addition, we evaluated the effects of PEG-IR780-C13 and NIR laser thermal ablation on normal renal tissue. The results showed that the uptake of PEG-IR780-C13 micelle. PEG-IR780-C13 by RENCA cells was mainly in lysosomes and late connotations of the cells. PEG-IR780-C13, irradiated by NIR laser, can efficiently convert light energy into heat energy, which can be used to kill RENCA cells and in situ renal tumors in mice. At the same time we found that PEG-IR780-C13 micelles and NIR laser thermal ablation of renal tumors can also lead to the damage of a small part of normal renal tissue around the renal tumor but this damage is very limited and does not lead to the damage of renal function in mice. Our results show that PEG-IR780-C13 and NIR laser-mediated photothermal effects can produce tumor-specific thermal energy to kill tumor tissue. This method provides a more minimally invasive method for the ablation of renal tumors. The radiosensitization effects of perfluorocarbons have been widely studied, but the need for additional oxygen supply before or during radiotherapy limits their use. In this study, perfluorohexane liposomes were synthesized for radiosensitization of renal cell carcinoma. After intravenous injection of perfluorohexane liposome, we found that perfluorohexane liposome accumulated in large quantities 24 hours after injection of perfluorohexane liposome by B-ultrasound and small animal imaging. Therefore, we injected perfluorohexane liposome 24 hours after normoxic irradiation of mice subcutaneously transplanted tumor X-ray. The mice were randomly divided into four groups: saline group, liposome group and liposome group. We evaluate the efficacy and safety of liposome radiosensitization by tumor volume and tumor histology. The results showed that the tumor growth of liposome X ray group was significantly slower than that of single X ray group, and the tumor apoptosis in liposome X ray group was significantly stronger than that in single X ray group. In addition, perfluorohexane liposomes had no significant collateral damage to other important organs. In conclusion, perfluorohexane liposomes can effectively concentrate on tumor sites and increase radiosensitivity to renal cell carcinoma under normoxic conditions.
【學(xué)位授予單位】：南京大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R943;R96

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