本文主要研究内容
作者姚志岗（2019）在《基于多功能纳米载体的药物可控递送与癌症饥饿治疗》一文中研究指出：传统化放疗手段难以区分肿瘤和正常组织器官,在癌症治疗过程中往往会引起严重的毒副作用和后遗症。纳米材料具有尺寸小、形貌可控、表面易修饰和生物相容性良好等优点,基于纳米材料构建的多功能纳米载体,可以实现药物的可控递送和刺激响应释放,提高药物递送效率的同时降低对正常组织的毒副作用。葡萄糖氧化酶(GOx)催化葡萄糖氧化过程可以消耗肿瘤内部的氧气和葡萄糖,最终引起肿瘤饥饿,是癌症饥饿治疗的理想药物。但毛细血管对肿瘤部位氧气和营养物质的持续供应和肿瘤乏氧微环境下GOx的低催化效率,使得单独依靠GOx的饥饿疗法很难完全消除肿瘤,因此开发新型的GOx协同治疗策略很有必要。本论文致力于利用纳米材料构建智能响应型多功能纳米载体并开发新型的癌症饥饿治疗策略,在提高癌症治疗效果的同时降低对正常组织的毒副作用,主要内容如下:1、级联适配体调控释放的包膜型多功能纳米载体用于HER2过表达乳腺癌靶向治疗利用纳米材料构建纳米载体是一种新颖的药物递送体系构建策略,但大多数已报道的纳米载体靶向性差,递送过程中会发生药物提前泄露,毒副作用较大。鉴于适配体的特异性识别功能和生物相容性,我们设计了一种级联适配体调控释放的包膜型多功能纳米载体,用于实现药物的靶向递送和刺激响应释放。纳米载体的构建使用了两种分别对HER2和ATP具有特异性识别能力的适配体,最外侧的HB5适配体可以靶向识别癌细胞表面过表达的HER2蛋白,而以ATP适配体为骨架构建的三元复合物内核(ternary complex,TC)可以在癌细胞内高浓度ATP的作用下逐渐解体,释放抗癌药物表没食子儿茶素没食子酸酯(EGCG)。纳米结构脂质体(NLC)对TC的包裹可以有效降低纳米载体在递送过程中由于药物过早泄漏引起的毒副作用,同时纳米载体完全由FDA批准通过的药物和生物分子构建而成,具有良好的生物相容性和生物降解性。该纳米载体采用了HB5和ATP适配体双靶向识别且结构单元稳定低毒,为高靶向性、高治疗效率和低毒副作用药物递送平台的设计提供了一种新颖的策略。2、透明质酸包裹的双催化功能纳米反应器用于调控细胞内氧化应激增益癌症饥饿治疗通过葡萄糖氧化酶(GOx)切断葡萄糖供应是一种新型的癌症饥饿治疗策略。但是单独使用GOx肿瘤抑制效果不佳,并且药物递送过程中存在损伤血管和正常器官的风险。为了提高纳米载体的治疗效率和对肿瘤的特异性,我们利用树枝状介孔硅对GOx和二茂铁的有效负载,设计了一种透明质酸(HA)包裹、细胞内特异性激活的双催化功能纳米反应器,用来调控细胞内氧化应激水平,增益癌症饥饿治疗效果。纳米反应器中负载的初级催化剂GOx可以有效地加速催化肿瘤内葡萄糖氧化成葡萄糖酸,同时产生H202,表面共价修饰的次级催化剂二茂铁可以通过芬顿反应将H202转化为更具细胞毒性的·OH。最外层的HA壳层不仅可以屏蔽递送过程中纳米反应器对血糖的催化氧化,最大程度地减小反应器对血管和正常组织的氧化损伤,而且可以赋予纳米反应器靶向进入CD44过表达肿瘤细胞的能力。进入细胞后,HA壳层被溶酶体中的透明质酸酶(HAase)降解,特异性地开启GOx和二茂铁介导的级联催化反应,加速葡萄糖的消耗和·OH的积累,进而通过饥饿和氧化协同治疗策略有效地杀死癌细胞、抑制肿瘤生长。该纳米载体采用级联催化反应提高了治疗效率,利用HA壳层的靶向与屏蔽功能降低了毒副作用,为开发高效低毒的协同治疗方案提供了一种新颖的纳米载体构建策略。
Abstract
chuan tong hua fang liao shou duan nan yi ou fen zhong liu he zheng chang zu zhi qi guan ,zai ai zheng zhi liao guo cheng zhong wang wang hui yin qi yan chong de du fu zuo yong he hou wei zheng 。na mi cai liao ju you che cun xiao 、xing mao ke kong 、biao mian yi xiu shi he sheng wu xiang rong xing liang hao deng you dian ,ji yu na mi cai liao gou jian de duo gong neng na mi zai ti ,ke yi shi xian yao wu de ke kong di song he ci ji xiang ying shi fang ,di gao yao wu di song xiao lv de tong shi jiang di dui zheng chang zu zhi de du fu zuo yong 。pu tao tang yang hua mei (GOx)cui hua pu tao tang yang hua guo cheng ke yi xiao hao zhong liu nei bu de yang qi he pu tao tang ,zui zhong yin qi zhong liu ji e ,shi ai zheng ji e zhi liao de li xiang yao wu 。dan mao xi xie guan dui zhong liu bu wei yang qi he ying yang wu zhi de chi xu gong ying he zhong liu fa yang wei huan jing xia GOxde di cui hua xiao lv ,shi de chan du yi kao GOxde ji e liao fa hen nan wan quan xiao chu zhong liu ,yin ci kai fa xin xing de GOxxie tong zhi liao ce lve hen you bi yao 。ben lun wen zhi li yu li yong na mi cai liao gou jian zhi neng xiang ying xing duo gong neng na mi zai ti bing kai fa xin xing de ai zheng ji e zhi liao ce lve ,zai di gao ai zheng zhi liao xiao guo de tong shi jiang di dui zheng chang zu zhi de du fu zuo yong ,zhu yao nei rong ru xia :1、ji lian kuo pei ti diao kong shi fang de bao mo xing duo gong neng na mi zai ti yong yu HER2guo biao da ru xian ai ba xiang zhi liao li yong na mi cai liao gou jian na mi zai ti shi yi chong xin ying de yao wu di song ti ji gou jian ce lve ,dan da duo shu yi bao dao de na mi zai ti ba xiang xing cha ,di song guo cheng zhong hui fa sheng yao wu di qian xie lou ,du fu zuo yong jiao da 。jian yu kuo pei ti de te yi xing shi bie gong neng he sheng wu xiang rong xing ,wo men she ji le yi chong ji lian kuo pei ti diao kong shi fang de bao mo xing duo gong neng na mi zai ti ,yong yu shi xian yao wu de ba xiang di song he ci ji xiang ying shi fang 。na mi zai ti de gou jian shi yong le liang chong fen bie dui HER2he ATPju you te yi xing shi bie neng li de kuo pei ti ,zui wai ce de HB5kuo pei ti ke yi ba xiang shi bie ai xi bao biao mian guo biao da de HER2dan bai ,er yi ATPkuo pei ti wei gu jia gou jian de san yuan fu ge wu nei he (ternary complex,TC)ke yi zai ai xi bao nei gao nong du ATPde zuo yong xia zhu jian jie ti ,shi fang kang ai yao wu biao mei shi zi er cha su mei shi zi suan zhi (EGCG)。na mi jie gou zhi zhi ti (NLC)dui TCde bao guo ke yi you xiao jiang di na mi zai ti zai di song guo cheng zhong you yu yao wu guo zao xie lou yin qi de du fu zuo yong ,tong shi na mi zai ti wan quan you FDApi zhun tong guo de yao wu he sheng wu fen zi gou jian er cheng ,ju you liang hao de sheng wu xiang rong xing he sheng wu jiang jie xing 。gai na mi zai ti cai yong le HB5he ATPkuo pei ti shuang ba xiang shi bie ju jie gou chan yuan wen ding di du ,wei gao ba xiang xing 、gao zhi liao xiao lv he di du fu zuo yong yao wu di song ping tai de she ji di gong le yi chong xin ying de ce lve 。2、tou ming zhi suan bao guo de shuang cui hua gong neng na mi fan ying qi yong yu diao kong xi bao nei yang hua ying ji zeng yi ai zheng ji e zhi liao tong guo pu tao tang yang hua mei (GOx)qie duan pu tao tang gong ying shi yi chong xin xing de ai zheng ji e zhi liao ce lve 。dan shi chan du shi yong GOxzhong liu yi zhi xiao guo bu jia ,bing ju yao wu di song guo cheng zhong cun zai sun shang xie guan he zheng chang qi guan de feng xian 。wei le di gao na mi zai ti de zhi liao xiao lv he dui zhong liu de te yi xing ,wo men li yong shu zhi zhuang jie kong gui dui GOxhe er mao tie de you xiao fu zai ,she ji le yi chong tou ming zhi suan (HA)bao guo 、xi bao nei te yi xing ji huo de shuang cui hua gong neng na mi fan ying qi ,yong lai diao kong xi bao nei yang hua ying ji shui ping ,zeng yi ai zheng ji e zhi liao xiao guo 。na mi fan ying qi zhong fu zai de chu ji cui hua ji GOxke yi you xiao de jia su cui hua zhong liu nei pu tao tang yang hua cheng pu tao tang suan ,tong shi chan sheng H202,biao mian gong jia xiu shi de ci ji cui hua ji er mao tie ke yi tong guo fen du fan ying jiang H202zhuai hua wei geng ju xi bao du xing de ·OH。zui wai ceng de HAke ceng bu jin ke yi bing bi di song guo cheng zhong na mi fan ying qi dui xie tang de cui hua yang hua ,zui da cheng du de jian xiao fan ying qi dui xie guan he zheng chang zu zhi de yang hua sun shang ,er ju ke yi fu yu na mi fan ying qi ba xiang jin ru CD44guo biao da zhong liu xi bao de neng li 。jin ru xi bao hou ,HAke ceng bei rong mei ti zhong de tou ming zhi suan mei (HAase)jiang jie ,te yi xing de kai qi GOxhe er mao tie jie dao de ji lian cui hua fan ying ,jia su pu tao tang de xiao hao he ·OHde ji lei ,jin er tong guo ji e he yang hua xie tong zhi liao ce lve you xiao de sha si ai xi bao 、yi zhi zhong liu sheng chang 。gai na mi zai ti cai yong ji lian cui hua fan ying di gao le zhi liao xiao lv ,li yong HAke ceng de ba xiang yu bing bi gong neng jiang di le du fu zuo yong ,wei kai fa gao xiao di du de xie tong zhi liao fang an di gong le yi chong xin ying de na mi zai ti gou jian ce lve 。
论文参考文献
论文详细介绍
论文作者分别是来自南京大学的姚志岗，发表于刊物南京大学2019-07-02论文，是一篇关于适配体论文,靶向递送论文,刺激响应论文,纳米结构脂质体论文,双催化功能纳米反应器论文,氧化应激论文,饥饿治疗论文,芬顿反应论文,南京大学2019-07-02论文的文章。本文可供学术参考使用，各位学者可以免费参考阅读下载，文章观点不代表本站观点，资料来自南京大学2019-07-02论文网站，若本站收录的文献无意侵犯了您的著作版权，请联系我们删除。
标签：适配体论文; 靶向递送论文; 刺激响应论文; 纳米结构脂质体论文; 双催化功能纳米反应器论文; 氧化应激论文; 饥饿治疗论文; 芬顿反应论文; 南京大学2019-07-02论文;