氧化石墨烯负载的戊柔比星抑制颅内黑色素瘤的增殖

发布时间：2019-05-07 08:45

【摘要】：癌症是威胁人类生命的主要疾病,尽管人们发展了多种物理和化学疗法,癌症患者的致死率仍居高不下。脑肿瘤特别是脑转移瘤,由于其特殊的位置和疾病的局限性,即使接受治疗,预后效果不佳且病人存活率非常低。因此,寻找和开发更有效的抗癌药物和相关疗法对于脑肿瘤的治疗和控制是极为重要的。本论文在前期药效筛选中发现,目前用于治疗乳腺癌和膀胱癌的天然来源药物戊柔比星(AD32)对小鼠黑色素瘤细胞B16也具有较强的生长抑制活性,但对小鼠颅内黑色素瘤的抗癌活性并不显著。由于AD32具有较大的π键,可以和石墨烯、碳纳米管等具有离域大π键的纳米材料通过π-π相互作用,形成纳米药物。因此,本论文考察了多壁碳纳米管(MWCNTs)和氧化石墨烯(GO)对AD32药效的影响。结果发现,MWCNTs和GO均可负载较大量的AD32,使AD32得到较好的缓释,并且其纳米复合药物均具有较强的细胞毒性。但是相同剂量的GO纳米复合药物的体内抗癌效果更好,且毒副作用最小。进一步的研究表明,AD32-GO以pH敏感性的方式缓慢释放AD32,而氧化石墨烯(GO)的参与加速药物进入细胞核的过程,增加肿瘤细胞对药物的吸收,降低肿瘤细胞耐药系统对药物的排出,从而增加活性氧ROS的生产,增强细胞毒性而不改变AD32使细胞周期受阻的特性,由此增强药物的体内外抗癌效果。因此,GO是一种安全有效的药物载体,而AD32-GO是一种安全有效的用于治疗脑肿瘤的纳米复合药物。
[Abstract]:Cancer is a major threat to human life, despite the development of a variety of physical and chemical therapies, the death rate of cancer patients remains high. Brain tumors, especially metastatic brain tumors, have poor prognosis and very low survival rate even after treatment because of their special location and limitations of the disease. Therefore, it is very important to find and develop more effective anticancer drugs and related therapies for the treatment and control of brain tumors. In this study, we found that pentarubicin (AD32), a natural drug used in the treatment of breast cancer and bladder cancer, also had strong growth inhibitory activity on mouse melanoma cell line B16. However, the antitumor activity against mouse intracranial melanoma was not significant. Because AD32 has a large 蟺 bond, it can interact with graphene, carbon nanotubes and other nano-materials with delocalized 蟺 bonds through 蟺-蟺 interaction to form nano-drugs. Therefore, the effects of multi-walled carbon nanotubes (MWCNTs) and graphene oxide (GO) on the efficacy of AD32 were investigated in this paper. The results showed that both MWCNTs and GO could load a large amount of AD32, to get better sustained release of AD32, and the nano-composite drugs had strong cytotoxicity. However, the anti-cancer effect of the same dose of GO nano-composite drug was better, and the toxicity and side-effect was the least. Further studies have shown that AD32-GO slowly releases AD32, in a pH-sensitive manner and graphene (GO) oxide is involved in accelerating the process of drug entry into the nucleus and increasing the absorption of drugs by tumor cells. In order to increase the production of reactive oxygen species (ROS) and enhance the cytotoxicity of tumor cells without changing the characteristics of AD32, the anti-cancer effect of the drug in vitro and in vivo can be enhanced by reducing the efflux of drug-resistant system of tumor cells. Therefore, GO is a safe and effective drug carrier, and AD32-GO is a safe and effective nano-composite drug for the treatment of brain tumors.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R739.41

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