本文主要研究内容
作者杜雾晨（2019）在《两亲性多肽P12的合成及其包载DOX特性研究》一文中研究指出：肿瘤已成为当今社会威胁人类生命的主要疾病之一,具有治愈难、死亡率高等特点。目前常用于肿瘤治疗的化疗法所使用的小分子化学药物往往具有副作用大、水溶性差等缺点,提高了肿瘤治疗的难度。因此,研发出一类可以解决以上问题的新型药物成为当务之急,但新型药物研发耗资大、时间长,为了更好更快的解决这些问题,药物载体材料应运而生。多肽因其良好的生物相容性及可降解性能成为备受研究者青睐的新型药物载体材料,而两亲性多肽由于其序列独特可以在水溶液中自发地形成自组装体,如胶束、纳米纤维、囊泡等,其中,具有独特“壳-核”结构的多肽纳米胶束在生物医学领域中已被广泛应用于抗肿瘤药物的载体。针对目前常用的抗肿瘤药物水溶性差、副作用大的现状,将具有自组装性能的小分子多肽作为载体,用于抗肿瘤药物阿霉素(DOX)的递送,以期增强药物的溶解性能,改善药物的控释及肿瘤靶向性能,具有重要的理论意义和应用价值。本论文设计并通过固相合成法制备两亲性小分子多肽(FFHFFH-KKGRGD,P12),其在水溶液中通过氢键和疏水作用驱动自组装形成具有包载能力的“核-壳”结构的纳米载体,可以包载水溶性较差的抗肿瘤药物DOX,形成多肽载DOX纳米胶束(P12&DOX),用于肿瘤治疗。采用透析法制备载阿霉素胶束,该合成方法简单易行且制备的P12&DOX纳米载药胶束的包封率(46.2%)和载药量(26.4%)较高,显著高于溶剂挥发法制备的产物,其包封率和载药量分别为28.8%和18.0%,且制备的纳米颗粒大小均一、粒径较小,平均粒径仅为120nm,小于溶剂挥发法制备的170nm。通过多次包载实验,确定P12包载DOX的最佳投料比为P12:DOX=4:1。通过模拟人体微环境来观察纳米载药胶束的释药情况,结果表明该纳米体系具有一定的酸敏特性;与市售阿霉素的释药效果进行对比试验表明P12&DOX载药胶束具有一定缓释能力。采用CCK-8法分别检测了P12、P12&DOX和DOX的细胞毒性,证明P12具有良好的生物相容性且对阿霉素具有一定的修饰作用,降低了其对正常细胞的损害。通过激光共聚焦显微镜观察正常细胞(HUVEC)与肿瘤细胞(4T1)对纳米载药胶束的摄取情况,结果表明4T1细胞比HUVEC细胞对P12&DOX纳米胶束的摄取量更多;纳米载药胶束能够更长时间的聚集在肿瘤组织周围,释放的药物能对肿瘤细胞造成更有效的杀伤。流式细胞仪定量观察细胞对载药颗粒的摄取与外排情况,进一步探究了P12&DOX纳米胶束作为抗肿瘤载药体系的可行性。
Abstract
zhong liu yi cheng wei dang jin she hui wei xie ren lei sheng ming de zhu yao ji bing zhi yi ,ju you zhi yu nan 、si wang lv gao deng te dian 。mu qian chang yong yu zhong liu zhi liao de hua liao fa suo shi yong de xiao fen zi hua xue yao wu wang wang ju you fu zuo yong da 、shui rong xing cha deng que dian ,di gao le zhong liu zhi liao de nan du 。yin ci ,yan fa chu yi lei ke yi jie jue yi shang wen ti de xin xing yao wu cheng wei dang wu zhi ji ,dan xin xing yao wu yan fa hao zi da 、shi jian chang ,wei le geng hao geng kuai de jie jue zhe xie wen ti ,yao wu zai ti cai liao ying yun er sheng 。duo tai yin ji liang hao de sheng wu xiang rong xing ji ke jiang jie xing neng cheng wei bei shou yan jiu zhe qing lai de xin xing yao wu zai ti cai liao ,er liang qin xing duo tai you yu ji xu lie du te ke yi zai shui rong ye zhong zi fa de xing cheng zi zu zhuang ti ,ru jiao shu 、na mi qian wei 、nang pao deng ,ji zhong ,ju you du te “ke -he ”jie gou de duo tai na mi jiao shu zai sheng wu yi xue ling yu zhong yi bei an fan ying yong yu kang zhong liu yao wu de zai ti 。zhen dui mu qian chang yong de kang zhong liu yao wu shui rong xing cha 、fu zuo yong da de xian zhuang ,jiang ju you zi zu zhuang xing neng de xiao fen zi duo tai zuo wei zai ti ,yong yu kang zhong liu yao wu a mei su (DOX)de di song ,yi ji zeng jiang yao wu de rong jie xing neng ,gai shan yao wu de kong shi ji zhong liu ba xiang xing neng ,ju you chong yao de li lun yi yi he ying yong jia zhi 。ben lun wen she ji bing tong guo gu xiang ge cheng fa zhi bei liang qin xing xiao fen zi duo tai (FFHFFH-KKGRGD,P12),ji zai shui rong ye zhong tong guo qing jian he shu shui zuo yong qu dong zi zu zhuang xing cheng ju you bao zai neng li de “he -ke ”jie gou de na mi zai ti ,ke yi bao zai shui rong xing jiao cha de kang zhong liu yao wu DOX,xing cheng duo tai zai DOXna mi jiao shu (P12&DOX),yong yu zhong liu zhi liao 。cai yong tou xi fa zhi bei zai a mei su jiao shu ,gai ge cheng fang fa jian chan yi hang ju zhi bei de P12&DOXna mi zai yao jiao shu de bao feng lv (46.2%)he zai yao liang (26.4%)jiao gao ,xian zhe gao yu rong ji hui fa fa zhi bei de chan wu ,ji bao feng lv he zai yao liang fen bie wei 28.8%he 18.0%,ju zhi bei de na mi ke li da xiao jun yi 、li jing jiao xiao ,ping jun li jing jin wei 120nm,xiao yu rong ji hui fa fa zhi bei de 170nm。tong guo duo ci bao zai shi yan ,que ding P12bao zai DOXde zui jia tou liao bi wei P12:DOX=4:1。tong guo mo ni ren ti wei huan jing lai guan cha na mi zai yao jiao shu de shi yao qing kuang ,jie guo biao ming gai na mi ti ji ju you yi ding de suan min te xing ;yu shi shou a mei su de shi yao xiao guo jin hang dui bi shi yan biao ming P12&DOXzai yao jiao shu ju you yi ding huan shi neng li 。cai yong CCK-8fa fen bie jian ce le P12、P12&DOXhe DOXde xi bao du xing ,zheng ming P12ju you liang hao de sheng wu xiang rong xing ju dui a mei su ju you yi ding de xiu shi zuo yong ,jiang di le ji dui zheng chang xi bao de sun hai 。tong guo ji guang gong ju jiao xian wei jing guan cha zheng chang xi bao (HUVEC)yu zhong liu xi bao (4T1)dui na mi zai yao jiao shu de she qu qing kuang ,jie guo biao ming 4T1xi bao bi HUVECxi bao dui P12&DOXna mi jiao shu de she qu liang geng duo ;na mi zai yao jiao shu neng gou geng chang shi jian de ju ji zai zhong liu zu zhi zhou wei ,shi fang de yao wu neng dui zhong liu xi bao zao cheng geng you xiao de sha shang 。liu shi xi bao yi ding liang guan cha xi bao dui zai yao ke li de she qu yu wai pai qing kuang ,jin yi bu tan jiu le P12&DOXna mi jiao shu zuo wei kang zhong liu zai yao ti ji de ke hang xing 。
论文参考文献
论文详细介绍
论文作者分别是来自安徽工程大学的杜雾晨，发表于刊物安徽工程大学2019-07-18论文，是一篇关于自组装论文,阿霉素论文,体外释药论文,细胞毒性论文,肿瘤靶向论文,安徽工程大学2019-07-18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，资料来自安徽工程大学2019-07-18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：自组装论文; 阿霉素论文; 体外释药论文; 细胞毒性论文; 肿瘤靶向论文; 安徽工程大学2019-07-18论文;