本文主要研究内容
作者李雪（2019）在《半乳糖化壳聚糖修饰的磁性介孔二氧化硅负载奈达铂纳米粒联合光热治疗的抗肿瘤研究》一文中研究指出：癌症是当今世界严重危害人类生命与健康的疾病之一,它分为多种类型,它的发病率和致死率均较高,目前,临床上治疗癌症的主要治疗手段有化疗、放疗、手术治疗、热疗（Hyperthermia,HT）、超声疗法等及将两种或者两种以上的治疗方法联合起来治疗癌症。因此,本课题拟构建半乳糖化壳聚糖（galactosylated chitosan,GC）修饰的磁性介孔二氧化硅（Magnetic mesoporous silica nanoparticles,MMSNs）负载奈达铂（Nedaplatin,NDP）的双重靶向给药系统（NDP@MMSN-COOH-GC NPs）,将该系统联合光热治疗（photothermal therapy,PTT）,具有以下优势:（1）半乳糖化壳聚糖修饰的磁性介孔二氧化硅载体的主动靶向作用使药物可以有效蓄积在肿瘤部位,减小全身毒性,提高生物安全性;（2）纳米载体凭借自身良好的光热效应,使得光热治疗大大增强了制剂的体内和体外抗肿瘤效果。相关研究如下:1、NDP@MMSN-COOH-GC NPs的制备与表征。采用共沉淀法制备水溶性Fe3O4。接着以Fe3O4为磁核,以正硅酸四乙酯为硅源,CTAB为模板剂,采用溶胶-凝胶法制备磁性介孔二氧化硅,并对MMSNs表面进行羧基化修饰,再以戊二醛作为交联剂,利用羧基可以和半乳糖化壳聚糖上的氨基作用,制备GC修饰的磁性介孔二氧化硅纳米粒子（MMSN-COOH-GC NPs）,通过红外,粒径电位,扫描电镜,透射电镜和氮气吸附-脱附等进行表征,并考察了纳米载体在808激光照射不同时间下的升温情况,最后以载药量和包封率为指标进行处方工艺的筛选,通过优化制剂制备的条件,最终得到具有双重靶向作用的NDP@MMSN-COOH-GC NPs制剂。红外光谱图显示Fe3O4磁核已被成功制备,MMSNs表面已经成功修饰上氨基和羧基,半乳糖化壳聚糖也已被成功包覆在MMSNs-COOH上;透射电子显微镜图显示,Fe3O4粒径为15 nm左右,MMSN–COOH NPs和MMSN–COOH–GC NPs粒径增至100 nm左右;Zeta电位图显示经柠檬酸钠修饰之后的Fe3O4的Zeta电位是-12.6 mV,此外,MMSNs表面成功修饰氨基后,电位为正,增加到+16.7 mV,而再次修饰羧基后,电位变为-21.8 mV,最后,MMSN-COOH NPs成功包覆GC后,电位变为+18.0 mV。磁性测试结果显示Fe3O4纳米粒子的饱和磁化值（Ms）为65 emu/g,具有超顺磁性,MMSN-COOH NPs和MMSN-COOH-GC NPs饱和磁化值分别为38 emu/g和28 emu/g;N2吸附-脱附曲线表明MMSN-COOH NPs的等温线符合IUPAC分类的IV型等温线,这说明MMSN-COOH NPs属于介孔材料。此外,通过BET法计算MMSN-COOH NPs的比表面积为568.80 m2/g,通过BJH计算其孔体积为1.15 cm3/g,孔径为6.3 nm。与超纯水对比,纳米载体在808激光的照射下均能够快速升温,在3分钟内,温度均可升至43℃以上,能达到光热治疗的目的。最后,经过各种条件筛选,最优处方所制备的NDP@MMSN-COOH-GC NPs,载药量为24.6%±1.34%,包封率为33.09%±1.22%。制剂的体外释放结果表明,NDP@MMSN–COOH–GC NPs组相比NDP@MMSN–COOH NPs一组,具有一定的缓释作用。此外,体外释药实验还表明在NIR激光的照射下由磁性纳米粒子产生的热量可以加速药物从制剂中释放。2、NDP@MMSN-COOH-GC NPs联合光热治疗的体外抗肿瘤活性研究。以人肺腺癌A549细胞为模型,进行一系列体外实验以研究NDP@MMSN-COOH-GC NPs制剂联合光热治疗的体外抗肿瘤活性及机制。细胞毒结果表明空白载体对A549细胞无明显毒性,此外,NDP@MMSNs-COOH-GC NPs联合光热治疗后可以更有效抑制肿瘤细胞的增殖;细胞摄取结果表明我们所构建的NDP@MMSNs-COOH-GC NPs载药系统可以更多的被A549细胞摄取;细胞周期实验结果表明NDP及其制剂（不）联合光热治疗和单独的光热治疗均能将A549细胞阻滞在S期,诱导细胞凋亡;细胞凋亡实验结果表明最终治疗组NDP@MMSNs-COOH-GC NPs+NIR laser的总凋亡率最高,远高于其他任何实验组,诱导了更多A549细胞的凋亡。上述结果说明NDP@MMSNs-COOH-GC NPs联合光热治疗可以有效的抑制肿瘤细胞的增殖,具有显著的体外抗肿瘤活性。3、NDP@MMSN-COOH-GC NPs联合光热治疗的体内抗肿瘤活性研究。以荷S180瘤的KM雌性小鼠为动物模型,进行一系列体内实验以研究NDP@MMSN-COOH-GC NPs制剂联合光热治疗的体内抗肿瘤效果。小动物活体成像结果显示,IR783@MMSN-COOH-GC NPs（肿瘤部位绑有磁铁）可以将药物有效靶向至肿瘤部位,24 h后肿瘤组织仍然有较强的荧光信号,证明了载体的靶向性。体内药效学结果显示NDP@MMSN-COOH-GC NPs+MT+NIR laser组有最好的治疗效果,抑瘤效果最佳。此外,有结果显示,相比奈达铂原料药组,其他各实验组小鼠的体重均未出现明显的下降趋势,说明制剂和载体均有较高的生物安全性。HE染色结果表明各组的心肝脾肺肾并未有明显的病理学改变,再次说明了制剂的安全性。但是肿瘤组织HE染色结果表明NDP@MMSN-COOH-GC NPs+MT+NIR laser组肿瘤细胞出现大部分凋亡坏死的现象,比其余几组更加明显。综合以上实验结果,证明本课题所制备的NDP@MMSN-COOH-GC NPs联合光热治疗能够有效抑制肿瘤增殖,且生物安全性良好。
Abstract
ai zheng shi dang jin shi jie yan chong wei hai ren lei sheng ming yu jian kang de ji bing zhi yi ,ta fen wei duo chong lei xing ,ta de fa bing lv he zhi si lv jun jiao gao ,mu qian ,lin chuang shang zhi liao ai zheng de zhu yao zhi liao shou duan you hua liao 、fang liao 、shou shu zhi liao 、re liao （Hyperthermia,HT）、chao sheng liao fa deng ji jiang liang chong huo zhe liang chong yi shang de zhi liao fang fa lian ge qi lai zhi liao ai zheng 。yin ci ,ben ke ti ni gou jian ban ru tang hua ke ju tang （galactosylated chitosan,GC）xiu shi de ci xing jie kong er yang hua gui （Magnetic mesoporous silica nanoparticles,MMSNs）fu zai nai da bo （Nedaplatin,NDP）de shuang chong ba xiang gei yao ji tong （NDP@MMSN-COOH-GC NPs）,jiang gai ji tong lian ge guang re zhi liao （photothermal therapy,PTT）,ju you yi xia you shi :（1）ban ru tang hua ke ju tang xiu shi de ci xing jie kong er yang hua gui zai ti de zhu dong ba xiang zuo yong shi yao wu ke yi you xiao xu ji zai zhong liu bu wei ,jian xiao quan shen du xing ,di gao sheng wu an quan xing ;（2）na mi zai ti ping jie zi shen liang hao de guang re xiao ying ,shi de guang re zhi liao da da zeng jiang le zhi ji de ti nei he ti wai kang zhong liu xiao guo 。xiang guan yan jiu ru xia :1、NDP@MMSN-COOH-GC NPsde zhi bei yu biao zheng 。cai yong gong chen dian fa zhi bei shui rong xing Fe3O4。jie zhao yi Fe3O4wei ci he ,yi zheng gui suan si yi zhi wei gui yuan ,CTABwei mo ban ji ,cai yong rong jiao -ning jiao fa zhi bei ci xing jie kong er yang hua gui ,bing dui MMSNsbiao mian jin hang suo ji hua xiu shi ,zai yi wu er quan zuo wei jiao lian ji ,li yong suo ji ke yi he ban ru tang hua ke ju tang shang de an ji zuo yong ,zhi bei GCxiu shi de ci xing jie kong er yang hua gui na mi li zi （MMSN-COOH-GC NPs）,tong guo gong wai ,li jing dian wei ,sao miao dian jing ,tou she dian jing he dan qi xi fu -tuo fu deng jin hang biao zheng ,bing kao cha le na mi zai ti zai 808ji guang zhao she bu tong shi jian xia de sheng wen qing kuang ,zui hou yi zai yao liang he bao feng lv wei zhi biao jin hang chu fang gong yi de shai shua ,tong guo you hua zhi ji zhi bei de tiao jian ,zui zhong de dao ju you shuang chong ba xiang zuo yong de NDP@MMSN-COOH-GC NPszhi ji 。gong wai guang pu tu xian shi Fe3O4ci he yi bei cheng gong zhi bei ,MMSNsbiao mian yi jing cheng gong xiu shi shang an ji he suo ji ,ban ru tang hua ke ju tang ye yi bei cheng gong bao fu zai MMSNs-COOHshang ;tou she dian zi xian wei jing tu xian shi ,Fe3O4li jing wei 15 nmzuo you ,MMSN–COOH NPshe MMSN–COOH–GC NPsli jing zeng zhi 100 nmzuo you ;Zetadian wei tu xian shi jing ning meng suan na xiu shi zhi hou de Fe3O4de Zetadian wei shi -12.6 mV,ci wai ,MMSNsbiao mian cheng gong xiu shi an ji hou ,dian wei wei zheng ,zeng jia dao +16.7 mV,er zai ci xiu shi suo ji hou ,dian wei bian wei -21.8 mV,zui hou ,MMSN-COOH NPscheng gong bao fu GChou ,dian wei bian wei +18.0 mV。ci xing ce shi jie guo xian shi Fe3O4na mi li zi de bao he ci hua zhi （Ms）wei 65 emu/g,ju you chao shun ci xing ,MMSN-COOH NPshe MMSN-COOH-GC NPsbao he ci hua zhi fen bie wei 38 emu/ghe 28 emu/g;N2xi fu -tuo fu qu xian biao ming MMSN-COOH NPsde deng wen xian fu ge IUPACfen lei de IVxing deng wen xian ,zhe shui ming MMSN-COOH NPsshu yu jie kong cai liao 。ci wai ,tong guo BETfa ji suan MMSN-COOH NPsde bi biao mian ji wei 568.80 m2/g,tong guo BJHji suan ji kong ti ji wei 1.15 cm3/g,kong jing wei 6.3 nm。yu chao chun shui dui bi ,na mi zai ti zai 808ji guang de zhao she xia jun neng gou kuai su sheng wen ,zai 3fen zhong nei ,wen du jun ke sheng zhi 43℃yi shang ,neng da dao guang re zhi liao de mu de 。zui hou ,jing guo ge chong tiao jian shai shua ,zui you chu fang suo zhi bei de NDP@MMSN-COOH-GC NPs,zai yao liang wei 24.6%±1.34%,bao feng lv wei 33.09%±1.22%。zhi ji de ti wai shi fang jie guo biao ming ,NDP@MMSN–COOH–GC NPszu xiang bi NDP@MMSN–COOH NPsyi zu ,ju you yi ding de huan shi zuo yong 。ci wai ,ti wai shi yao shi yan hai biao ming zai NIRji guang de zhao she xia you ci xing na mi li zi chan sheng de re liang ke yi jia su yao wu cong zhi ji zhong shi fang 。2、NDP@MMSN-COOH-GC NPslian ge guang re zhi liao de ti wai kang zhong liu huo xing yan jiu 。yi ren fei xian ai A549xi bao wei mo xing ,jin hang yi ji lie ti wai shi yan yi yan jiu NDP@MMSN-COOH-GC NPszhi ji lian ge guang re zhi liao de ti wai kang zhong liu huo xing ji ji zhi 。xi bao du jie guo biao ming kong bai zai ti dui A549xi bao mo ming xian du xing ,ci wai ,NDP@MMSNs-COOH-GC NPslian ge guang re zhi liao hou ke yi geng you xiao yi zhi zhong liu xi bao de zeng shi ;xi bao she qu jie guo biao ming wo men suo gou jian de NDP@MMSNs-COOH-GC NPszai yao ji tong ke yi geng duo de bei A549xi bao she qu ;xi bao zhou ji shi yan jie guo biao ming NDPji ji zhi ji （bu ）lian ge guang re zhi liao he chan du de guang re zhi liao jun neng jiang A549xi bao zu zhi zai Sji ,you dao xi bao diao wang ;xi bao diao wang shi yan jie guo biao ming zui zhong zhi liao zu NDP@MMSNs-COOH-GC NPs+NIR laserde zong diao wang lv zui gao ,yuan gao yu ji ta ren he shi yan zu ,you dao le geng duo A549xi bao de diao wang 。shang shu jie guo shui ming NDP@MMSNs-COOH-GC NPslian ge guang re zhi liao ke yi you xiao de yi zhi zhong liu xi bao de zeng shi ,ju you xian zhe de ti wai kang zhong liu huo xing 。3、NDP@MMSN-COOH-GC NPslian ge guang re zhi liao de ti nei kang zhong liu huo xing yan jiu 。yi he S180liu de KMci xing xiao shu wei dong wu mo xing ,jin hang yi ji lie ti nei shi yan yi yan jiu NDP@MMSN-COOH-GC NPszhi ji lian ge guang re zhi liao de ti nei kang zhong liu xiao guo 。xiao dong wu huo ti cheng xiang jie guo xian shi ,IR783@MMSN-COOH-GC NPs（zhong liu bu wei bang you ci tie ）ke yi jiang yao wu you xiao ba xiang zhi zhong liu bu wei ,24 hhou zhong liu zu zhi reng ran you jiao jiang de ying guang xin hao ,zheng ming le zai ti de ba xiang xing 。ti nei yao xiao xue jie guo xian shi NDP@MMSN-COOH-GC NPs+MT+NIR laserzu you zui hao de zhi liao xiao guo ,yi liu xiao guo zui jia 。ci wai ,you jie guo xian shi ,xiang bi nai da bo yuan liao yao zu ,ji ta ge shi yan zu xiao shu de ti chong jun wei chu xian ming xian de xia jiang qu shi ,shui ming zhi ji he zai ti jun you jiao gao de sheng wu an quan xing 。HEran se jie guo biao ming ge zu de xin gan pi fei shen bing wei you ming xian de bing li xue gai bian ,zai ci shui ming le zhi ji de an quan xing 。dan shi zhong liu zu zhi HEran se jie guo biao ming NDP@MMSN-COOH-GC NPs+MT+NIR laserzu zhong liu xi bao chu xian da bu fen diao wang huai si de xian xiang ,bi ji yu ji zu geng jia ming xian 。zeng ge yi shang shi yan jie guo ,zheng ming ben ke ti suo zhi bei de NDP@MMSN-COOH-GC NPslian ge guang re zhi liao neng gou you xiao yi zhi zhong liu zeng shi ,ju sheng wu an quan xing liang hao 。
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论文作者分别是来自郑州大学的李雪，发表于刊物郑州大学2019-07-03论文，是一篇关于磁性介孔二氧化硅论文,肺腺癌论文,光热治疗论文,奈达铂论文,半乳糖化壳聚糖论文,郑州大学2019-07-03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，资料来自郑州大学2019-07-03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：磁性介孔二氧化硅论文; 肺腺癌论文; 光热治疗论文; 奈达铂论文; 半乳糖化壳聚糖论文; 郑州大学2019-07-03论文;