本文主要研究内容
作者胡希（2019）在《酸响应功能放大型纳米药物的构建及其抗肿瘤性能研究》一文中研究指出：随着药剂学和纳米技术的交叉发展,抗肿瘤纳米药物递送系统得到广泛而深入的研究。如何提高纳米药物的肿瘤治疗效果,同时降低对正常组织的毒副作用是抗肿瘤纳米药物的研究热点之一。金属纳米材料凭借优越的化学和物理(热、光、声和磁等)特性,具备自身固有的抗肿瘤活性、抗肿瘤药物递送性能、成像诊断性能等,因此在抗肿瘤新型疗法、多模态协同治疗以及可视化治疗等方面具有巨大的潜力。本论文首先合成并使用酸响应型高分子,包覆金属抗肿瘤纳米材料(以具备酸响应溢出毒性离子性能的超小铂纳米簇为例),得到一种在肿瘤部位酸响应放大抗肿瘤活性,且有效降低对正常组织毒副作用的酸响应功能放大型铂基纳米药物(Pt-NA)。通过研究对比发现,小尺寸铂纳米簇在酸性环境中响应溢出毒性铂离子(Pt2+)。粒径和透光率结果显示Pt-NA具备酸响应性。其在中性环境中以纳米聚集体形式存在,在酸性环境中响应解体为铂纳米簇。细胞研究结果显示,Pt-NA不仅对顺铂耐药SP+CD24+LM3肝癌细胞(干细胞样细胞)有更强的细胞毒性,而且能够有效抑制肿瘤干细胞样细胞的成球性。体内抗肿瘤研究表明,Pt-NA组瘤体的抑制效果和坏死程度均显著强于顺铂组和索拉菲尼组。HE染色和血生化研究结果均显示,Pt-NA未引起肝脏、肾脏等器官毒性,具有良好的生物相容性。另外,临床上需通过影像学手段诊断肿瘤、评估治疗效果、调整治疗方案以及预后复查等。整合靶向递送、药物治疗、活体示踪和疗效监测等诸多功能于一体的抗肿瘤纳米诊疗体系是目前的研究趋势之一。因此,本研究进一步将肿瘤成像与肿瘤治疗结合,开发一类可视化酸响应放大抗肿瘤活性,可经肾清除并有效降低对正常组织毒副作用的多模态抗肿瘤纳米诊疗药物。本研究基于金属可视化抗肿瘤纳米材料(以具备高X射线吸收性能的超小碳酸氧铋纳米簇为例),使用溶剂热法得到一种集CT成像、放疗增敏、化疗药物递送和经肾排泄于一体的可视化酸响应功能放大型铋基纳米药物(BNTs)。细胞研究结果显示,BNTs吸收X射线后产生活性氧(ROS)并造成肿瘤细胞DNA损伤,展现出优越的放疗增敏性能。另外,BNTs能够负载阿霉素(DOX)等小分子化疗药物,且在肿瘤酸性环境中解体并释放药物,酸响应型放大抗肿瘤功能。体内研究结果证实,中空管状BNTs能够高效富集于肿瘤部位,并通过CT成像实现肿瘤部位可视化。细胞和体内研究结果发现,与单一放疗或化疗方法相比,BNTs/DOX介导的放化疗多模态治疗显著提高肿瘤细胞内ROS水平并损伤细胞核内DNA,最终诱导肿瘤细胞凋亡并显著抑制肿瘤生长。此外,TEM和排泄研究结果表明,BNTs在肿瘤酸性环境中响应解体为BNCs,随后通过肾脏途径随尿液排出体外。细胞和体内研究结果均验证,BNTs具备良好的生物相容性。本论文通过化学合成和药剂学手段分别以超小铂纳米簇为金属抗肿瘤纳米材料,以碳酸氧铋纳米簇为金属可视化抗肿瘤纳米材料,构建一系列肿瘤酸性环境响应放大治疗功能,并且有效降低对正常组织毒副作用的高效、安全的响应型抗肿瘤纳米药物。本论文将为设计和开发在肿瘤部位选择性激活抗肿瘤活性,同时对机体安全、无毒的智能型抗肿瘤纳米药物递送系统提供思路和可行性方案。
Abstract
sui zhao yao ji xue he na mi ji shu de jiao cha fa zhan ,kang zhong liu na mi yao wu di song ji tong de dao an fan er shen ru de yan jiu 。ru he di gao na mi yao wu de zhong liu zhi liao xiao guo ,tong shi jiang di dui zheng chang zu zhi de du fu zuo yong shi kang zhong liu na mi yao wu de yan jiu re dian zhi yi 。jin shu na mi cai liao ping jie you yue de hua xue he wu li (re 、guang 、sheng he ci deng )te xing ,ju bei zi shen gu you de kang zhong liu huo xing 、kang zhong liu yao wu di song xing neng 、cheng xiang zhen duan xing neng deng ,yin ci zai kang zhong liu xin xing liao fa 、duo mo tai xie tong zhi liao yi ji ke shi hua zhi liao deng fang mian ju you ju da de qian li 。ben lun wen shou xian ge cheng bing shi yong suan xiang ying xing gao fen zi ,bao fu jin shu kang zhong liu na mi cai liao (yi ju bei suan xiang ying yi chu du xing li zi xing neng de chao xiao bo na mi cu wei li ),de dao yi chong zai zhong liu bu wei suan xiang ying fang da kang zhong liu huo xing ,ju you xiao jiang di dui zheng chang zu zhi du fu zuo yong de suan xiang ying gong neng fang da xing bo ji na mi yao wu (Pt-NA)。tong guo yan jiu dui bi fa xian ,xiao che cun bo na mi cu zai suan xing huan jing zhong xiang ying yi chu du xing bo li zi (Pt2+)。li jing he tou guang lv jie guo xian shi Pt-NAju bei suan xiang ying xing 。ji zai zhong xing huan jing zhong yi na mi ju ji ti xing shi cun zai ,zai suan xing huan jing zhong xiang ying jie ti wei bo na mi cu 。xi bao yan jiu jie guo xian shi ,Pt-NAbu jin dui shun bo nai yao SP+CD24+LM3gan ai xi bao (gan xi bao yang xi bao )you geng jiang de xi bao du xing ,er ju neng gou you xiao yi zhi zhong liu gan xi bao yang xi bao de cheng qiu xing 。ti nei kang zhong liu yan jiu biao ming ,Pt-NAzu liu ti de yi zhi xiao guo he huai si cheng du jun xian zhe jiang yu shun bo zu he suo la fei ni zu 。HEran se he xie sheng hua yan jiu jie guo jun xian shi ,Pt-NAwei yin qi gan zang 、shen zang deng qi guan du xing ,ju you liang hao de sheng wu xiang rong xing 。ling wai ,lin chuang shang xu tong guo ying xiang xue shou duan zhen duan zhong liu 、ping gu zhi liao xiao guo 、diao zheng zhi liao fang an yi ji yu hou fu cha deng 。zheng ge ba xiang di song 、yao wu zhi liao 、huo ti shi zong he liao xiao jian ce deng zhu duo gong neng yu yi ti de kang zhong liu na mi zhen liao ti ji shi mu qian de yan jiu qu shi zhi yi 。yin ci ,ben yan jiu jin yi bu jiang zhong liu cheng xiang yu zhong liu zhi liao jie ge ,kai fa yi lei ke shi hua suan xiang ying fang da kang zhong liu huo xing ,ke jing shen qing chu bing you xiao jiang di dui zheng chang zu zhi du fu zuo yong de duo mo tai kang zhong liu na mi zhen liao yao wu 。ben yan jiu ji yu jin shu ke shi hua kang zhong liu na mi cai liao (yi ju bei gao Xshe xian xi shou xing neng de chao xiao tan suan yang bi na mi cu wei li ),shi yong rong ji re fa de dao yi chong ji CTcheng xiang 、fang liao zeng min 、hua liao yao wu di song he jing shen pai xie yu yi ti de ke shi hua suan xiang ying gong neng fang da xing bi ji na mi yao wu (BNTs)。xi bao yan jiu jie guo xian shi ,BNTsxi shou Xshe xian hou chan sheng huo xing yang (ROS)bing zao cheng zhong liu xi bao DNAsun shang ,zhan xian chu you yue de fang liao zeng min xing neng 。ling wai ,BNTsneng gou fu zai a mei su (DOX)deng xiao fen zi hua liao yao wu ,ju zai zhong liu suan xing huan jing zhong jie ti bing shi fang yao wu ,suan xiang ying xing fang da kang zhong liu gong neng 。ti nei yan jiu jie guo zheng shi ,zhong kong guan zhuang BNTsneng gou gao xiao fu ji yu zhong liu bu wei ,bing tong guo CTcheng xiang shi xian zhong liu bu wei ke shi hua 。xi bao he ti nei yan jiu jie guo fa xian ,yu chan yi fang liao huo hua liao fang fa xiang bi ,BNTs/DOXjie dao de fang hua liao duo mo tai zhi liao xian zhe di gao zhong liu xi bao nei ROSshui ping bing sun shang xi bao he nei DNA,zui zhong you dao zhong liu xi bao diao wang bing xian zhe yi zhi zhong liu sheng chang 。ci wai ,TEMhe pai xie yan jiu jie guo biao ming ,BNTszai zhong liu suan xing huan jing zhong xiang ying jie ti wei BNCs,sui hou tong guo shen zang tu jing sui niao ye pai chu ti wai 。xi bao he ti nei yan jiu jie guo jun yan zheng ,BNTsju bei liang hao de sheng wu xiang rong xing 。ben lun wen tong guo hua xue ge cheng he yao ji xue shou duan fen bie yi chao xiao bo na mi cu wei jin shu kang zhong liu na mi cai liao ,yi tan suan yang bi na mi cu wei jin shu ke shi hua kang zhong liu na mi cai liao ,gou jian yi ji lie zhong liu suan xing huan jing xiang ying fang da zhi liao gong neng ,bing ju you xiao jiang di dui zheng chang zu zhi du fu zuo yong de gao xiao 、an quan de xiang ying xing kang zhong liu na mi yao wu 。ben lun wen jiang wei she ji he kai fa zai zhong liu bu wei shua ze xing ji huo kang zhong liu huo xing ,tong shi dui ji ti an quan 、mo du de zhi neng xing kang zhong liu na mi yao wu di song ji tong di gong sai lu he ke hang xing fang an 。
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论文详细介绍
论文作者分别是来自浙江大学的胡希，发表于刊物浙江大学2019-07-05论文，是一篇关于酸响应论文,功能放大论文,金属纳米材料论文,肿瘤治疗论文,生物相容性论文,浙江大学2019-07-05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，资料来自浙江大学2019-07-05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：酸响应论文; 功能放大论文; 金属纳米材料论文; 肿瘤治疗论文; 生物相容性论文; 浙江大学2019-07-05论文;