本文主要研究内容
作者刘晶（2019）在《肿瘤微环境调控的纳米载体用于药物递送的研究》一文中研究指出：纳米药物在体内面临体液、肿瘤微环境和细胞等多重屏障,极大地影响纳米载体递送药物的效率,限制其在体内的应用。纳米载体的特性影响其在药物不同输送阶段的效应,进而影响总体的药物递送效率和肿瘤治疗效果。如何设计并发展在药物体内输送各个环节特性可变的纳米载体,对于提高药物输送效率和最大化抗肿瘤效应有至关重要的意义。利用肿瘤部位特殊的微环境可以实现在不同递送阶段对纳米载体特性的调控。本论文集中研究利用肿瘤微酸性环境对纳米载体的性能(包括表面电势、尺寸等)的调控,并进一步研究调控后的特性对于纳米载体在肿瘤部位诱发的生物学效应,例如其在肿瘤的渗透、细胞内化、转运过程以及对抗肿瘤和抗转移的影响。本论文的研究内容主要分为以下三个部分:1、发展基于肿瘤酸度激活的快速电荷反转的纳米载体UCC-NP3/Pt,其中,PAEMA嵌段在生理pH值下形成疏水核心,并且PCEA嵌段的羧基可以有效地荷载顺铂。肿瘤组织低pH环境使得PAEMA阻滞的叔胺基团快速质子化,在10 s内产生快速电荷转换,有效增强颗粒在肿瘤细胞的内化效率,实现了药物的靶向递送,在顺铂耐药肿瘤模型中表现出优异的抗肿瘤效果。2、基于前期发展的一种在肿瘤酸度响应下发生尺寸转变从而提高纳米颗粒在原发瘤渗透的iCluster递送系统,在本工作中,利用iCluster平台在原发肿瘤中具有强大穿透能力的小尺寸纳米颗粒可以渗入肿瘤淋巴管并转运至淋巴结。定量分析和荧光成像实验证明iCluster能够在原发性肿瘤的存在下实现对肿瘤前哨淋巴结的显像和药物递送。结合iCluster化疗和原发瘤手术切除的联合策略对小鼠的乳腺癌进行早期干预,可以延长小鼠的存活周期;在小鼠晚期转移性乳腺癌模型中,iCluster亦能够显著抑制肺转移和延长生存周期。3、基于iCluster递送平台在血液循环中保持100nm左右的尺度,在肿瘤部位释放小尺度颗粒的特性,构建具有相似的尺寸和电势的G3-、G5-和G7-iCluster。由于其药代动力学和初始肿瘤富集量的相似性,在肿瘤组织中不同尺寸的PAMAM从iCluster释放下来。结果表明细微尺寸变化会显著影响其在肿瘤的行为,G5-iCluster在原位胰腺肿瘤模型中的治疗效果优于G3-iCluster和G7-iCluster。进一步研究表明G3-PAMAM由于其小尺寸和弱的细胞内化而在肿瘤组织中具有较低的颗粒滞留,而G7-PAMAM较大的尺寸和颗粒与细胞强的相互作用而导致其穿透性差。相反,G5-PAMAM表现出综合的肿瘤渗透、细胞内化和肿瘤滞留性能。本研究揭示微小尺寸差异对小尺度纳米颗粒的瘤内行为有着显著影响。
Abstract
na mi yao wu zai ti nei mian lin ti ye 、zhong liu wei huan jing he xi bao deng duo chong bing zhang ,ji da de ying xiang na mi zai ti di song yao wu de xiao lv ,xian zhi ji zai ti nei de ying yong 。na mi zai ti de te xing ying xiang ji zai yao wu bu tong shu song jie duan de xiao ying ,jin er ying xiang zong ti de yao wu di song xiao lv he zhong liu zhi liao xiao guo 。ru he she ji bing fa zhan zai yao wu ti nei shu song ge ge huan jie te xing ke bian de na mi zai ti ,dui yu di gao yao wu shu song xiao lv he zui da hua kang zhong liu xiao ying you zhi guan chong yao de yi yi 。li yong zhong liu bu wei te shu de wei huan jing ke yi shi xian zai bu tong di song jie duan dui na mi zai ti te xing de diao kong 。ben lun wen ji zhong yan jiu li yong zhong liu wei suan xing huan jing dui na mi zai ti de xing neng (bao gua biao mian dian shi 、che cun deng )de diao kong ,bing jin yi bu yan jiu diao kong hou de te xing dui yu na mi zai ti zai zhong liu bu wei you fa de sheng wu xue xiao ying ,li ru ji zai zhong liu de shen tou 、xi bao nei hua 、zhuai yun guo cheng yi ji dui kang zhong liu he kang zhuai yi de ying xiang 。ben lun wen de yan jiu nei rong zhu yao fen wei yi xia san ge bu fen :1、fa zhan ji yu zhong liu suan du ji huo de kuai su dian he fan zhuai de na mi zai ti UCC-NP3/Pt,ji zhong ,PAEMAqian duan zai sheng li pHzhi xia xing cheng shu shui he xin ,bing ju PCEAqian duan de suo ji ke yi you xiao de he zai shun bo 。zhong liu zu zhi di pHhuan jing shi de PAEMAzu zhi de shu an ji tuan kuai su zhi zi hua ,zai 10 snei chan sheng kuai su dian he zhuai huan ,you xiao zeng jiang ke li zai zhong liu xi bao de nei hua xiao lv ,shi xian le yao wu de ba xiang di song ,zai shun bo nai yao zhong liu mo xing zhong biao xian chu you yi de kang zhong liu xiao guo 。2、ji yu qian ji fa zhan de yi chong zai zhong liu suan du xiang ying xia fa sheng che cun zhuai bian cong er di gao na mi ke li zai yuan fa liu shen tou de iClusterdi song ji tong ,zai ben gong zuo zhong ,li yong iClusterping tai zai yuan fa zhong liu zhong ju you jiang da chuan tou neng li de xiao che cun na mi ke li ke yi shen ru zhong liu lin ba guan bing zhuai yun zhi lin ba jie 。ding liang fen xi he ying guang cheng xiang shi yan zheng ming iClusterneng gou zai yuan fa xing zhong liu de cun zai xia shi xian dui zhong liu qian shao lin ba jie de xian xiang he yao wu di song 。jie ge iClusterhua liao he yuan fa liu shou shu qie chu de lian ge ce lve dui xiao shu de ru xian ai jin hang zao ji gan yu ,ke yi yan chang xiao shu de cun huo zhou ji ;zai xiao shu wan ji zhuai yi xing ru xian ai mo xing zhong ,iClusteryi neng gou xian zhe yi zhi fei zhuai yi he yan chang sheng cun zhou ji 。3、ji yu iClusterdi song ping tai zai xie ye xun huan zhong bao chi 100nmzuo you de che du ,zai zhong liu bu wei shi fang xiao che du ke li de te xing ,gou jian ju you xiang shi de che cun he dian shi de G3-、G5-he G7-iCluster。you yu ji yao dai dong li xue he chu shi zhong liu fu ji liang de xiang shi xing ,zai zhong liu zu zhi zhong bu tong che cun de PAMAMcong iClustershi fang xia lai 。jie guo biao ming xi wei che cun bian hua hui xian zhe ying xiang ji zai zhong liu de hang wei ,G5-iClusterzai yuan wei yi xian zhong liu mo xing zhong de zhi liao xiao guo you yu G3-iClusterhe G7-iCluster。jin yi bu yan jiu biao ming G3-PAMAMyou yu ji xiao che cun he ruo de xi bao nei hua er zai zhong liu zu zhi zhong ju you jiao di de ke li zhi liu ,er G7-PAMAMjiao da de che cun he ke li yu xi bao jiang de xiang hu zuo yong er dao zhi ji chuan tou xing cha 。xiang fan ,G5-PAMAMbiao xian chu zeng ge de zhong liu shen tou 、xi bao nei hua he zhong liu zhi liu xing neng 。ben yan jiu jie shi wei xiao che cun cha yi dui xiao che du na mi ke li de liu nei hang wei you zhao xian zhe ying xiang 。
论文参考文献
论文详细介绍
论文作者分别是来自中国科学技术大学的刘晶，发表于刊物中国科学技术大学2019-07-12论文，是一篇关于药物输送系统论文,纳米特性论文,肿瘤微环境响应论文,肿瘤治疗论文,中国科学技术大学2019-07-12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，资料来自中国科学技术大学2019-07-12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：药物输送系统论文; 纳米特性论文; 肿瘤微环境响应论文; 肿瘤治疗论文; 中国科学技术大学2019-07-12论文;