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类型 基础研究 预答辩日期 2018-05-09
开始(开题)日期 2016-12-05 论文结束日期 2018-03-22
地点 东南大学化学化工学院老楼319 论文选题来源 国家自然科学基金项目     论文字数 5.5 (万字)
题目 具有靶向和智能释放功能的铂类药物运载模型研究
主题词 肿瘤微环境,靶向,智能释放,铂类药物,药物传递
摘要 铂类小分子药物是一类被广泛应用于多种一线临床癌症治疗的活性物质。铂类药物具有较好的细胞毒性和肿瘤抑制能力,其中,顺铂对睾丸癌的临床抑制率高达百分之九十,使其得到了广泛的认可。然而,较为严重的毒副作用,较低的生物相容性以及长期用药后产生的细胞耐药性等问题统统限制了铂类药物的抗肿瘤活性功能进一步发挥。因此,如何提高铂类药物的肿瘤细胞抑制效率,减少其糟糕的体内分布,增强特异性肿瘤细胞摄取等方面成为了药物工作者重要研究的对象。 本文首先详述了铂类药物的发展脉络,介绍铂类药物的细胞作用机制,常见的毒副作用,细胞对铂类药物反应的生理过程。其次,简要地梳理了经典的铂(II)和铂(IV)小分子化合物的研究现状,论述了其存在的优点和不足,以及最近被广泛研究的,可以应用于铂类药物传递的纳米载体的相关研究。最后,我们提出了利用靶向性物质、肿瘤微环境特点、聚合物或者纳米粒子的较好传递性质等作为一种方法途径,用来增强药物的靶向性,智能释放能力等,以此来提高铂类药物的治疗效率和安全性。 随后,我们详细的列举了关于这方面的研究工作。其中,我们设计具有特异性识别肿瘤细胞高表达的豆荚蛋白酶的聚合物载药模型。其通过肽链与蛋白酶的高亲合性,在识别、内吞以及智能释放方面表现出较好的性质。我们制备了两种不同类型的载有光热材料的聚合物纳米粒子模型,该类纳米粒子不仅具有其本身较好的生物相容性、稳定性,对铂药分子具有较好的保护等优点,同时,在靶向性物质以及光热材料的帮助下,其对肿瘤细胞具有较好的亲合性以及治疗活性。我们合成了一种无机硅材料为骨架的纳米粒子,通过其中的金核与相变材料物质,强化了纳米粒子对药物的控制释放能力,其同样具有较好的靶向性以及细胞抑制能力。 综上所示,我们在保留经典抗肿瘤细胞分子药物活性的同时,借鉴了最新的针对肿瘤细胞自身特性进行选择性抑制和最新的纳米粒子载药模型研究成果等设计思路,在提高药物的细胞毒性以及减少其毒副作用方面开展了一系列工作,希望能够对铂类药物的更好的发展具有一定作用。
英文题目 STUDY OF THE TARGETED, CONTROLLED-RELEASED DELIVERY VECTOR FOR PLATINUM DRUGS
英文主题词 Microenvironment of cancer cell, Targeting, Controlled-release, Platinum-based drugs, Drug delivery
英文摘要 Platinum-based drugs are widely used as a master key in the multiple cancer therapies, as the curative ratio of cisplatin against testicular carcinoma which was received extensive satisfaction and interest. However, the adverse side effects during the in vivo circulation, the relatively weak biocompatibility and the arisen tolerance limit the further application of the platinum-based drugs. To settle the aforementioned problems, many investigators foucs on how to improve the anticancer ability and reduce the side effects of platinum-based drugs. The thesis firstly elaborates the development of the platinum-based drugs, including the mechanism of effect upon the cells by platinum-based drugs; the common side effects of platinum-based drugs; the response of cell against platinum-based drugs. Then, we briefly present the studies upon the platinum (II)-based or platinum (IV)-based small molecular drugs, state the advantages and disadvantages of the small molecular drugs. We also present the recent development of nanotechnology applied into the drug transportation. Finally, we elaborate our insight upon taking advantage of the targeting materials, microenvironment of cancer and smart properties of polymer or nanospheres to structure the platinum-loaded drug-transport system with the specific recognition and controlled-released abiliy. Subsequently, we respectively introduce the works upon the platinum-loaded drug-transport system with the specific recognition and controlled-released abiliy. We prepare a series of polymer-platinum conjugates by utilizing the “stealth” polyethylene glycol and legumain-cleavable oligopeptide. The synthesized polymer-platinum conjugates exhibiting great potential in avoiding the side effects and enhancing the therapy ability. We synthesize two kinds of cisplatin-loaded nanospheres with different NIR photothermal materials. The nanospheres exhibit great potential in avoiding the side effects and enhancing the therapy ability of cisplatin with the assistance of photothermal and targeting materials. We fabricated cisplatin and 1-tetradecanol loaded mesoporous silica-coated gold nanoframes. The gold inner and 1-tetradecanol strengthen the controlled-released ability of platinum complex; in the meantime, the nanospheres also exhibit great potential in avoiding the side effects and enhancing the therapy ability. In conclusion, we take advantage of polymer or nanosphere for maintaining the original cytotoxicity of platinum-based drug and improving its anticancer ability and reducing the side effects by conjugating the targeting materials and empolying controlled-released mechanism. We hope the works would be helpful to the development of platinum-based drugs.
学术讨论
主办单位时间地点报告人报告主题
东南大学化学化工学院 2015-7-23 化工楼319 施天一 cRGD/TAT dual-ligand reversibly cross-linked micelles loaded with docetaxel penetrate deeply into tumor tissue and show high antitumor efficacy in vivo
东南大学化学化工学院 2016-04-15 化工楼319 游朝群 Enhanced cytotoxicity by a benzothiazole containing cisplatin derivative in breast cells
东南大学化学化工学院 2016-08-08 化工楼319 施天一 Dual-peptide-functionalized albumin-based nanoparticles with pH-dependent self-assembly behavior for drug delivery
东南大学化学化工学院 2016-11-20 化工楼319 游朝群 Near-Infrared Light and pH Dual-Responsive Targeted Drug Carrier Based on Core-Crosslinked Polyaniline Nanoparticles for Intracellular Delivery of Cisplatin
东南大学化学化工学院 2017-04-15 化工楼319 施天一 Fullerene (C60)-based tumor-targeting nanoparticles with “off-on” state
东南大学化学化工学院 2017-07-23 化工楼319 游朝群 A strategy for photothermal conversion of polymeric nanoparticles by polyaniline for smart control of targeted drug delivery
东南大学化学化工学院 2017-09-28 化工楼319 施天一 cRGD-functionalized reduction-sensitive shell-sheddable biodegradable micelles mediate enhanced doxorubicin delivery to human glioma xenografts in vivo
东南大学化学化工学院 2017-12-30 化工楼319 游朝群 Co-delivery of cisplatin and CJM-126 via photothermal conversion nanoparticles for enhanced synergistic antitumor efficacy
     
学术会议
会议名称时间地点本人报告本人报告题目
国家自然科学基金委员会 2016/10/13-10/16 上海-上海师范大学 特异性酶识别与释放功能的聚合物-铂(Ⅱ)偶联物的研究
国家自然科学基金委员会 2017/09/23-09/26 武汉-华中师范大学 特异性酶识别与光热智能释放纳米载药模型研究
     
代表作
论文名称
A series of enzyme-controlled-release polymer-platinum-based drug conjugates for the treatment of ga
Enhanced legumain-recognition and NIR controlled released of cisplatinindocyanine
 
答辩委员会组成信息
姓名职称导师类别工作单位是否主席备注
王飞 正高 教授 博导 南京林业大学
朱进 正高 教授 博导 南京医科大学
孙岳明 正高 教授 博导 东南大学
王明亮 正高 教授 博导 东南大学
周钰明 正高 教授 博导 东南大学
      
答辩秘书信息
姓名职称工作单位备注
罗洋辉 其他 讲师 东南大学