【摘要】：癌癥是威脅人類生命的主要疾病,盡管人們發(fā)展了多種物理和化學(xué)療法,癌癥患者的致死率仍居高不下。腦腫瘤特別是腦轉(zhuǎn)移瘤,由于其特殊的位置和疾病的局限性,即使接受治療,預(yù)后效果不佳且病人存活率非常低。因此,尋找和開發(fā)更有效的抗癌藥物和相關(guān)療法對(duì)于腦腫瘤的治療和控制是極為重要的。本論文在前期藥效篩選中發(fā)現(xiàn),目前用于治療乳腺癌和膀胱癌的天然來源藥物戊柔比星(AD32)對(duì)小鼠黑色素瘤細(xì)胞B16也具有較強(qiáng)的生長(zhǎng)抑制活性,但對(duì)小鼠顱內(nèi)黑色素瘤的抗癌活性并不顯著。由于AD32具有較大的π鍵,可以和石墨烯、碳納米管等具有離域大π鍵的納米材料通過π-π相互作用,形成納米藥物。因此,本論文考察了多壁碳納米管(MWCNTs)和氧化石墨烯(GO)對(duì)AD32藥效的影響。結(jié)果發(fā)現(xiàn),MWCNTs和GO均可負(fù)載較大量的AD32,使AD32得到較好的緩釋,并且其納米復(fù)合藥物均具有較強(qiáng)的細(xì)胞毒性。但是相同劑量的GO納米復(fù)合藥物的體內(nèi)抗癌效果更好,且毒副作用最小。進(jìn)一步的研究表明,AD32-GO以pH敏感性的方式緩慢釋放AD32,而氧化石墨烯(GO)的參與加速藥物進(jìn)入細(xì)胞核的過程,增加腫瘤細(xì)胞對(duì)藥物的吸收,降低腫瘤細(xì)胞耐藥系統(tǒng)對(duì)藥物的排出,從而增加活性氧ROS的生產(chǎn),增強(qiáng)細(xì)胞毒性而不改變AD32使細(xì)胞周期受阻的特性,由此增強(qiáng)藥物的體內(nèi)外抗癌效果。因此,GO是一種安全有效的藥物載體,而AD32-GO是一種安全有效的用于治療腦腫瘤的納米復(fù)合藥物。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R739.41

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