基于蒙药“阿拉嘎-斑布”定向非小细胞肺癌的输送系统的研究

The traditional Mongolian medicine deem mylabris has the efficacy of discharge pulse, the diuretic, antivirus.Modern medicine has proved natural toxins - cantharidin and the bound cantharidin can treat cancer,However, its clinical application is limited because of its irritating effect on human mucosal system.This project proposed a new drug delivery system which can deliver the Pharmacodynamic substances to the tumor site in vivo .The Pharmacodynamic substances including cantharidin and the bound cantharidin,etc are extracted from cantharis and can treat cancer. The basic ideas of establishing the system of the long circulating liposome is peptide YSA modified in nanoliposome surface, the corporate loading of insoluble and soluble Pharmacodynamic substances .And the YSA-liposome can bind Specific EphA2 receptor on surface of A549,as a result the nanoliposome transport into lung cancer nonsmall-cell A549.This study explores the possibility that nano-drug delivery system of Pharmacodynamic substances based on cantharis of Mongolian can deliver to tumor and targeting tumor cell and exert anticancer effect and reduce toxic side effects .The use of surface plasmon resonance (SPR), laser confocal microscopy, in vivo imaging and other modern medical methods illustrate that the system based on cantharis of mongolian drug can effectively target and kill tumor while the system can reduce toxic side effects and discuss other related scientific problems .The system based on mongolian drug's Pharmacodynamic substances demonstrate great significance in targeting delivery for anticancer.This programm has good novelty, strong research power, scientific research conditions, and has carried out some preliminary research, the preliminary results show that the feasibility of the item is good.

蒙医认为阿拉嘎-斑布（斑蝥）具有泄脉、利尿、杀毒之功效。现代医学证明斑蝥体内的天然毒素-斑蝥素（难溶）与结合斑蝥素（易溶）抗癌有确切疗效，然而其对人体的粘膜系统的刺激性，很大程度上限制了临床应用。本项目提出一种能够将斑蝥体内斑蝥素与结合斑蝥素共同输送到肿瘤部位的新型纳米载药系统，构建该系统的思路是将长循环脂质体表面用配体YSA修饰，并同时载装斑蝥体内的斑蝥素与结合斑蝥素，表面修饰YSA的长循环纳米脂质体能够和非小细胞肺癌细胞A549表面的EphA2受体特异性结合，并被转运入癌细胞内部。本研究探索该载药系统作为蒙药阿拉嘎-斑布体内抗癌药效物质靶向递送的可能性和可以降低药物毒副作用等。利用表面等离子共振技术、激光共聚焦、活体成像等现代医学手段阐明该系统对肿瘤及肿瘤细胞的靶向性、杀伤性及相关科学问题，该系统作为基于蒙药药效物质的靶向递送具有重要意义。本项目已进行了部分前期研究，结果显示可行性良好

蒙药“阿拉噶-班布”对许多癌症均有确切疗效，然而有效成分斑蝥素对粘膜系统等有很强的刺激性，并且斑蝥素本身不溶于水很难被有效利用，虽然通过普通表面活性剂去增溶斑蝥素可以增加斑蝥素的溶解度和生物利用度，然而这种方法并不能有效的去改善斑蝥素药物的传递功能或靶向性，即不能很好地解决药物的组织分布特异性或靶向递送的作用。本项目针对蒙药“阿拉噶-班布”药效成分难溶性斑蝥素，通过纳米给药系统将斑蝥素等进行载药或包封，并对药物粒子进行表面修饰，使其具有靶向A549肿瘤细胞的功能，课题通过开展基于蒙药“阿拉噶-班布”的抗肿瘤研究，在解决了斑蝥素的溶解度问题的基础上(最高可达1mg/ml)，使其具有靶向特定肿瘤细胞表面marker功能的药物。

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