基于纳米药物递送系统的肾癌新治疗手段的探索与应用

发布时间：2018-04-25 02:17

本文选题：近红外染料 + IR780　；参考：《南京大学》2016年博士论文

【摘要】：本研究中我们利用小鼠原位肾肿瘤模型探索了PEG-IR780-C13及NIR激光用于热消融肾肿瘤的可行性。另外,我们还评估了PEG-IR780-C13及NIR激光热消融肾肿瘤时对于正常肾组织的影响。体外实验结果表明,RENCA细胞主要通过小窝介导的内吞作用摄取PEG-IR780-C13胶束。PEG-IR780-C13被RENCA细胞摄取之后主要分布于细胞的溶酶体及晚期内涵体中。在NIR激光的照射下,PEG-IR780-C13能够高效地将光能转化为热能,用于杀伤RENCA细胞以及小鼠原位肾肿瘤。同时我们发现PEG-IR780-C13胶束及NIR激光热消融肾肿瘤同时也会导致肾肿瘤周围小部分正常肾组织的损伤,但这一损伤非常局限,并未导致小鼠肾功能的损害。我们的实验结果表明,PEG-IR780-C13及NIR激光介导的光热效应能够产生肿瘤特异性的热能杀伤肿瘤组织。这一方法为临床提供了一种更加微创的热消融肾肿瘤的方法。全氟化碳制剂的放疗增敏作用曾被广泛研究,但是放疗前或放疗时需要额外供氧限制了其使用。本研究合成全氟己烷脂质体用于肾癌放疗增敏。尾静脉注射全氟己烷脂质体后,我们通过B超及小动物成像发现,全氟己烷脂质体注射24小时后在瘤内大量聚集。所以,我们在注射全氟己烷脂质体24小时后常氧下对小鼠皮下移植瘤进行X射线照射。实验小鼠随机分为四组：生理盐水组、脂质体组、X线组、脂质体+X线组。我们通过肿瘤体积和肿瘤组织学来评估脂质体放疗增敏的效果及安全性。结果显示,脂质体+X线组小鼠肿瘤生长明显比单独X线组延缓,组织染色显示脂质体+X线组小鼠肿瘤凋亡明显强于单独X线组。另外,全氟己烷脂质体对其他重要脏器组织没有明显副损伤。总之,全氟己烷脂质体能有效聚集于肿瘤部位并在常氧下增加肾癌放疗敏感性。
[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.
【学位授予单位】：南京大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R943;R96

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