基于磁热疗法的cRGD介导的超顺磁长循环纳米脂质体用于维吾尔药去氢骆驼蓬碱抗癌及其对癌细胞p53基因的研究

项目名称： 基于磁热疗法的cRGD介导的超顺磁长循环纳米脂质体用于维吾尔药去氢骆驼蓬碱抗癌及其对癌细胞p53基因的研究

项目编号： No.81460539

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王梅

作者单位： 新疆医科大学

项目金额： 43万元

中文摘要： 为使维吾尔药抗癌成分去氢骆驼蓬碱更好地靶向癌细胞，减少其毒副作用，本研究拟首次构建一种cRGD修饰的去氢骆驼蓬碱超顺磁长循环多功能脂质体。该脂质体将超顺磁纳米粒包裹入长循环脂质体，同时包裹维吾尔药抗癌成分去氢骆驼蓬碱，并在脂质体表面偶联RDG肽。利用磁纳米粒的磁靶向作用，在外部磁场下，将脂质体靶向到肿瘤细胞，又利用cRGD与肿瘤表面αγβ3受体的结合，使系统主动靶向到肿瘤细胞，并利用磁热效应，在肿瘤部位使脂质体膜破裂，药物释放，从而杀灭癌细胞。该磁纳米脂质体，可使磁纳米粒在肿瘤部位富集，克服磁纳米粒在肿瘤部位浓度低的问题，同时利用脂质体表面修饰达到磁纳米粒的长循环作用，还提高药物靶向性，降低其毒副作用。本研究对脂质体的可行性从体外和体内进行考察。另外针对去氢骆驼蓬碱对神经系统的毒性，利用脑胶质细胞瘤为模型细胞，考察去氢骆驼蓬碱及脂质体对脑癌的作用。并考察其对肿瘤细胞p53基因的作用机制。

中文关键词： 磁性脂质体；超顺磁纳米粒；去氢骆驼蓬碱；脂质体；肿瘤靶向

英文摘要： In order to target cancer cells and decrease side effects of harmine, a uygur anti-cancer drugs, A kind of cRGD modified magnetoliposomes which encapsulates ultrasmall superparamagetic nanoparticles(USPIOs) and harmine into its aqueous core will be studied. This kind of magnetoliposomes will entrap not only USPIOs but also harmine which is a kind of common Uygur anti-cancer drugs, and cRGD peptide will be conjugated with the lipid at the out of the space of liposomes, because cRGD will be highly expressed in cancer cells. This kind of magnetoliposomes owns several functions at the same time. One is that it can target to cancer cells with the aid of external magnetic fields and can serve as MRI contrast agents. Another function is that it can actively target to cancer cells because cRGD at the surface of this magnetoliposme can bind with αγβ3 existing the cancer cells.And also this kind of magnetoliposomes can increase the content of USPIOs at the tumor sites and prolong the mean residual time of USPIOs.So it can overcome some disadvantages of USPIOs when it is used in clinic. When this magnetoliposomes reach to cancer cells, it will burst out becuase the magnetical effects creat heat and lead to membrane of liposomes breaks, and then harmine will release and kill cancer cells,which is named as hyperthermia. If that, harmine will focus on cancer cells because of this targeting delivery system and subsequently kill cancer cells after this kind of magnetoliposomes enter the cancer cells, which will decrease the side effect of harmine on the nervous system. So this drug delivery system is a multifuntional preparation. In this study, we will focus on the characteristics of magnetoliposomes in vitro and in vivo through detecting DLS, entrap efficiency, cell intake, cell apoptosis,MTT etc. And we also want to be know if harmine can kill brain tumor cells since harmine has strong side effects on brain when it is used. Futhermore, we are also want to concentrate on the anti-cancer mechanism of harmine and its magnetoliposomes through cell and molecular biology experiments such as Western-blot and RT-PCR,especially their effects on p53 gene because there are few researchers who are studying its anti-cancer mechanism.

英文关键词： magnetoliposomes;superparamagnetic iron oxide nanoparticles;harmine;liposome;tumor targeted