本文主要研究内容
作者贺港(2019)在《可注射型水凝胶用于肿瘤热化疗的研究》一文中研究指出:肿瘤边界术中精确界定是目前临床中的挑战性难题,患者的肿瘤病灶部位往往因为未完全清除肿瘤细胞而导致复发和转移。另一方面,术后的创口组织非常脆弱,往往容易堆积大量的组织液,从而滋生细菌,引起更为严重的炎症反应。针对癌症临床手术风险大,易出血,易感染,易复发,手术创口不规则难以粘附和包埋等缺陷,本论文提出了利用可注射型高粘附性水凝胶进行术后热化疗防止肿瘤再生的创新性思路。受贻贝启发,本论文选择了具有类儿茶酚结构的没食子酸以及表面带正电荷的天然抗菌止血材料壳聚糖为原料,通过没食子酸对壳聚糖进行可溶性改性制备出壳聚糖交联没食子酸(CSG)前驱体。利用CSG前驱体负载DOX后再与Fe3+鳌合,从而得到具有粘附、抗菌、消炎、止血、抗肿瘤特性的可注射型CSG/Fe3+水凝胶。此外,实体肿瘤组织内不规则的血管系统、组织间液高压成为目前化疗药物进入肿瘤的主要障碍。通过将可注射型水凝胶直接注入肿瘤部位,能够在提高化疗效率的同时降低全身的毒副反应。由亲水性高分子通过一定的化学或物理交联形成的水凝胶,被认为是此类治疗药物的有效载体。然而,目前分子型水凝胶材料仍存在控制药物释放能力不强,药物低浓度缓慢释放易引起肿瘤耐药性等弱点,限制了其临床应用。针对目前分子型水凝胶材料存在合成复杂、引入交联剂及可控性有待提高的难题,本论文制备了一种基于由溶液pH诱导的纳米粒子电荷反转而形成的均相可注射水凝胶。该方法适用于不同位置的恶性肿瘤治疗,且其所采用的构建材料均为生物相容可降解材料,具有良好的临床应用前景。本文主要内容及结论分为以下两部分:1)我们通过一个简单的酰胺反应制备CSG前驱体,该CSG前驱体不仅具有良好的水溶性,而且具有抗肿瘤、抗炎症、抗菌等功能性作用。进一步的,我们合成了CSG/Fe3+水凝胶,该水凝胶可注射,自愈合性能良好,同时兼具优异的细胞相容性,其在pH为6的磷酸盐缓冲液中,具有高达200%的吸水溶胀率。通过组织粘附剂的剪切搭接测试,其润湿状态下的组织粘附力达7.2 Kpa。通过大鼠肝脏止血模型证明了CSG/Fe3+水凝胶超强的止血性能。将CSG前驱体于溶解于DOX水溶液,再与Fe3+鳌合便可以得到一种具有强组织粘附剂与止血功能的抗肿瘤缓释植入剂,我们通过小鼠4T1肿瘤模型验证了其通过热化疗联合治疗治愈肿瘤的能力。2)明胶蛋白粒子表面带电性质具有pH依赖性,我们通过引入D-葡萄糖酸-δ-内酯水解调控溶液的pH值,使得明胶蛋白粒子(Gela NPs)在其等电点附近发生电荷的反转,与带负电的类黑色素聚多巴胺粒子(PDA NPs)构建均一的Gela/PDA胶体凝胶。该水凝胶生物可降解,且具有良好的粘弹性、生物相容性和自愈合能力,能够成功包载化疗药物阿霉素,实现肿瘤微环境(酸性及高浓度基质金属蛋白酶2/9)及近红外激光响应的药物控制释放,实现肿瘤的局部热化疗联合治疗。
Abstract
zhong liu bian jie shu zhong jing que jie ding shi mu qian lin chuang zhong de tiao zhan xing nan ti ,huan zhe de zhong liu bing zao bu wei wang wang yin wei wei wan quan qing chu zhong liu xi bao er dao zhi fu fa he zhuai yi 。ling yi fang mian ,shu hou de chuang kou zu zhi fei chang cui ruo ,wang wang rong yi dui ji da liang de zu zhi ye ,cong er zi sheng xi jun ,yin qi geng wei yan chong de yan zheng fan ying 。zhen dui ai zheng lin chuang shou shu feng xian da ,yi chu xie ,yi gan ran ,yi fu fa ,shou shu chuang kou bu gui ze nan yi nian fu he bao mai deng que xian ,ben lun wen di chu le li yong ke zhu she xing gao nian fu xing shui ning jiao jin hang shu hou re hua liao fang zhi zhong liu zai sheng de chuang xin xing sai lu 。shou yi bei qi fa ,ben lun wen shua ze le ju you lei er cha fen jie gou de mei shi zi suan yi ji biao mian dai zheng dian he de tian ran kang jun zhi xie cai liao ke ju tang wei yuan liao ,tong guo mei shi zi suan dui ke ju tang jin hang ke rong xing gai xing zhi bei chu ke ju tang jiao lian mei shi zi suan (CSG)qian qu ti 。li yong CSGqian qu ti fu zai DOXhou zai yu Fe3+ao ge ,cong er de dao ju you nian fu 、kang jun 、xiao yan 、zhi xie 、kang zhong liu te xing de ke zhu she xing CSG/Fe3+shui ning jiao 。ci wai ,shi ti zhong liu zu zhi nei bu gui ze de xie guan ji tong 、zu zhi jian ye gao ya cheng wei mu qian hua liao yao wu jin ru zhong liu de zhu yao zhang ai 。tong guo jiang ke zhu she xing shui ning jiao zhi jie zhu ru zhong liu bu wei ,neng gou zai di gao hua liao xiao lv de tong shi jiang di quan shen de du fu fan ying 。you qin shui xing gao fen zi tong guo yi ding de hua xue huo wu li jiao lian xing cheng de shui ning jiao ,bei ren wei shi ci lei zhi liao yao wu de you xiao zai ti 。ran er ,mu qian fen zi xing shui ning jiao cai liao reng cun zai kong zhi yao wu shi fang neng li bu jiang ,yao wu di nong du huan man shi fang yi yin qi zhong liu nai yao xing deng ruo dian ,xian zhi le ji lin chuang ying yong 。zhen dui mu qian fen zi xing shui ning jiao cai liao cun zai ge cheng fu za 、yin ru jiao lian ji ji ke kong xing you dai di gao de nan ti ,ben lun wen zhi bei le yi chong ji yu you rong ye pHyou dao de na mi li zi dian he fan zhuai er xing cheng de jun xiang ke zhu she shui ning jiao 。gai fang fa kuo yong yu bu tong wei zhi de e xing zhong liu zhi liao ,ju ji suo cai yong de gou jian cai liao jun wei sheng wu xiang rong ke jiang jie cai liao ,ju you liang hao de lin chuang ying yong qian jing 。ben wen zhu yao nei rong ji jie lun fen wei yi xia liang bu fen :1)wo men tong guo yi ge jian chan de xian an fan ying zhi bei CSGqian qu ti ,gai CSGqian qu ti bu jin ju you liang hao de shui rong xing ,er ju ju you kang zhong liu 、kang yan zheng 、kang jun deng gong neng xing zuo yong 。jin yi bu de ,wo men ge cheng le CSG/Fe3+shui ning jiao ,gai shui ning jiao ke zhu she ,zi yu ge xing neng liang hao ,tong shi jian ju you yi de xi bao xiang rong xing ,ji zai pHwei 6de lin suan yan huan chong ye zhong ,ju you gao da 200%de xi shui rong zhang lv 。tong guo zu zhi nian fu ji de jian qie da jie ce shi ,ji run shi zhuang tai xia de zu zhi nian fu li da 7.2 Kpa。tong guo da shu gan zang zhi xie mo xing zheng ming le CSG/Fe3+shui ning jiao chao jiang de zhi xie xing neng 。jiang CSGqian qu ti yu rong jie yu DOXshui rong ye ,zai yu Fe3+ao ge bian ke yi de dao yi chong ju you jiang zu zhi nian fu ji yu zhi xie gong neng de kang zhong liu huan shi zhi ru ji ,wo men tong guo xiao shu 4T1zhong liu mo xing yan zheng le ji tong guo re hua liao lian ge zhi liao zhi yu zhong liu de neng li 。2)ming jiao dan bai li zi biao mian dai dian xing zhi ju you pHyi lai xing ,wo men tong guo yin ru D-pu tao tang suan -δ-nei zhi shui jie diao kong rong ye de pHzhi ,shi de ming jiao dan bai li zi (Gela NPs)zai ji deng dian dian fu jin fa sheng dian he de fan zhuai ,yu dai fu dian de lei hei se su ju duo ba an li zi (PDA NPs)gou jian jun yi de Gela/PDAjiao ti ning jiao 。gai shui ning jiao sheng wu ke jiang jie ,ju ju you liang hao de nian dan xing 、sheng wu xiang rong xing he zi yu ge neng li ,neng gou cheng gong bao zai hua liao yao wu a mei su ,shi xian zhong liu wei huan jing (suan xing ji gao nong du ji zhi jin shu dan bai mei 2/9)ji jin gong wai ji guang xiang ying de yao wu kong zhi shi fang ,shi xian zhong liu de ju bu re hua liao lian ge zhi liao 。
论文参考文献
论文详细介绍
论文作者分别是来自合肥工业大学的贺港,发表于刊物合肥工业大学2019-09-20论文,是一篇关于手术治疗论文,热化疗论文,抗肿瘤论文,水凝胶论文,水凝胶论文,合肥工业大学2019-09-20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,资料来自合肥工业大学2019-09-20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:手术治疗论文; 热化疗论文; 抗肿瘤论文; 水凝胶论文; 合肥工业大学2019-09-20论文;