CN112516332B - 一种荧光/pH/温敏/磁性多重响应的纳米凝胶载体及其制备方法 - Google Patents
一种荧光/pH/温敏/磁性多重响应的纳米凝胶载体及其制备方法 Download PDFInfo
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Abstract
本文公开发明了一种荧光/pH/温敏/磁性多重响应的纳米凝胶载体及其制备方法。包括如下步骤:以N‑异丙基丙烯酰胺(NIPAM)和聚丙烯酸(PAA)为温度和pH响应性单体,以磁流体为磁响应性单体,二乙烯基苯(DVB)为交联剂,加入环糊精(β‑CD),通过细乳液聚合法制备出磁性纳米凝胶。将磁性纳米凝胶活化后,通过氨羧络合反应在磁性纳米凝胶表面键合实验室自制的石墨烯量子点(NH2‑GQDs)得到荧光/pH/温敏/磁性多重响应的纳米凝胶。本发明的荧光/pH/温敏/磁性多重响应的纳米凝胶保留了优良的粒径和良好的分散性,在加入NH2‑GQDs量为40μl时,不仅具有良好的磁响应强度而且具有最佳荧光响应性能。
Description
技术领域
本发明涉及纳米材料领,负载药物控制释放领域,具体涉及一种荧光/pH/温敏/磁性多重响应的纳米凝胶载体及其制备方法。
背景技术
癌症是每年造成大量人群死亡的灾害之一,尽管已有不少药物如阿霉素(DOX)和甲氨蝶呤(MTX)被广泛用于癌症临床治疗,但耐药性导致疗效较低,需注射大剂量药物,对人体造成极大危害。所以用于药物输送与可控释放的智能纳米凝胶的生物安全性非常重要。
采用β-CD改性构筑药物分子负载、输送和缓释的载体,载体本身往往具有一定的药物分子负载、输送和缓释性能,β-CD单元的引入不仅可以通过包结络合作用提升药物分子的负载量,同时起到缓释的作用,β-CD单元的引入还可以显著降低该药物分子负载、输送和缓释体系的细胞毒性,提高其生物兼容性。由于载体的存在,在负载、输送和缓释药物分子的同时,可以负载DNA或siRNA,甚至靶向输送配体,因此,可以将多种具有疗效的药物分子同时、靶向输送的病变部位,并控制性缓慢释放,起到协同治疗、高效治疗的效果。
申请人已经申请的专利CN201510452707公布了一种水热法制备石墨烯量子点(NH2-GQDs)的方法,量子点粒径在1.5-10 nm,有优异的发光性能和高稳定性,只需要少量的石墨烯量子点(NH2-GQDs)就可以产生荧光信号可以顺利的进行荧光成像。毒性较低适用于生物***。优良的水溶性能,不需要表面改性。可以作为一种新型荧光二维碳纳米材料,有望构建具有载药、示踪显像等多功能的纳米载药平台。
磁性纳米凝胶是一种纳米尺寸并具有核-壳结构的磁性高分子复合材料,内核为磁性Fe3O4磁性纳米微粒,外层为磁性高分子纳米水凝胶,兼有内核的磁响应性能及外层水凝胶的生物相容性和可修饰性等特点,磁性纳米凝胶具有广泛的应用前景。
磁性/荧光纳米凝胶同时拥有发光特性和磁性,可广泛应用于磁共振成像、细胞标记和分选等重要领域。通过外部刺激(磁响应性)可以精准且主动将药物主动靶向患者的病变部位。
目前,尚未有一种荧光/pH/温敏/磁性多重响应的纳米凝胶的研究或报道。本发明开发了一种具有良好稳定性和生物相容性、具有靶向功能的荧光/pH/温敏/磁性多重响应的纳米凝胶。
发明内容
本发明的目的是提供一种荧光/pH/温敏/磁性多重响应的纳米凝胶的制备方法,该方法制备的荧光/pH/温敏/磁性多重响应的纳米凝胶呈均匀网络结构且分布均匀、具有良好的粒径。
为达到本发明的目的,本发明的技术方案包括以下步骤:①以N-异丙基丙烯酰胺(NIPAM)和聚丙烯酸(PAA)为温度和pH响应性单体,以磁流体为磁响应性单体,二乙烯基苯(DVB)为交联剂,加入环糊精(β-CD),通过细乳液聚合法制备出磁性纳米凝胶。②将磁性纳米凝胶活化后,通过氨羧络合反应在磁性纳米凝胶表面键合实验室自制的NH2-GQDs得到荧光/pH/温敏/磁性多重响应的纳米凝胶。
具体步骤为:
步骤1:以N-异丙基丙烯酰胺(NIPAM)和聚丙烯酸(PAA)为温度和pH响应性单体,以磁流体为磁响应性单体,二乙烯基苯(DVB)为交联剂,加入环糊精(β-CD),通过细乳液聚合法制备出磁性纳米凝胶。
A、称取0.128~0.130g NIPAM、0.008~0.010g PAA、0.03~0.05g SDS、0.1700~0.1800gβ-CD并溶于90~110ml 蒸馏水中,记作水相。取一个25mL的小烧杯,称取0.07~0.09g MAPEG和0.0197~0.0199g DVB溶于4~6ml二甲基亚砜(DMSO)中,记作油相。将油相采用注射泵(3.5mL/h)加入水相,同时进行超声,滴加结束后再次超声,计时2~3h。称取1.4~1.6g的磁流体,采用相同的方法滴加于水相中,滴加结束后再次超声2~3h。采用超声破碎机进行细乳化15~25min(300W),得细乳化液。
B、将细乳化液转置三口烧瓶中,通氮气10~20min,将水浴锅加热到65~75℃后加入0.006~0.008gKPS,通氮气10~20min,持续反应过夜,将制备产物用M=14000的透析袋透析3天,所得样品即为磁性纳米凝胶。
步骤2:将磁性纳米凝胶活化后,通过氨羧络合反应在磁性纳米凝胶表面键合实验室自制的NH2-GQDs得到荧光/pH/温敏/磁性多重响应的纳米凝胶。
A、取磁性纳米凝胶溶液14~16ml,称取0.0085~0.0087g N-羟基琥珀酰亚胺(NHS),放置于25℃的全温振荡培养箱,振荡25~35min。
B、振荡结束后,称取0.009~0.011g 二亚酰胺酸盐(EDC)加入到混合液中继续振荡1.5~2.5h,加入10~60μl的NH2-GQDs,避光振荡11~13h,即得荧光/pH/温敏/磁性多重响应的纳米凝胶。
本发明所取得的有益成果:
(1)本发明成功采用细乳液聚合法制备出了磁性纳米凝胶,并且键合了NH2-GQDs,合成出荧光/pH/温敏/磁性多重响应的纳米凝胶,加入的β-CD提高了荧光/pH/温敏/磁性多重响应的纳米凝胶的溶解度、稳定性,减小了荧光/pH/温敏/磁性多重响应的纳米凝胶的刺激性,降低药物毒副作用,并且可以调节药物释放速度,提高生物利用度。
(2)本发明成功合成的荧光/pH/温敏/磁性多重响应的纳米凝胶在加入的NH2-GQDs量在40μl时,粒径分布均匀并具有最佳的荧光响应性,并且键合上的NH2-GQDs不影响磁响应强度。
附图说明
图1为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的红外谱图。
图2为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的粒径分析图。
图3为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的扫描电镜图。
图4为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的透射电镜图。
图5为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的温度响应性图。
图6为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的pH响应图。
图7为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的磁响应图谱。
图8为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的荧光光谱图。
图9为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的荧光光谱图。
具体实施方式
以下结合实施例对本发明做进一步说明,但下述实施例对本发明的保护范围并无明确限制。
NH2-GQDs的制备:
称取2g三硝基苯、量取5ml氨水和40ml水合肼,倒入到一个烧杯中进行混合,混合好的溶液倒入三口烧瓶并在超声的条件下搅拌0.5h。将超声结束的悬浮液倒入聚四氟乙烯管中(管2/3处即可),装好后再将聚四氟乙烯管放到高压反应釜里,置于箱式电阻炉中进行200℃水热处理9h。反应结束后,取出高压反应釜(注意高温),再将其冷却至室温。冷却至室温后,将高压反应釜里的聚四氟乙烯管取出,再将里面的溶液用针管吸出,再用0.22μm的微孔滤膜过滤,最终得到的溶液即为NH2-GQDs。准备一个干净的小烧杯,用锡纸将其包裹得以避光,然后将滤好的NH2-GQDs倒入其中,用保鲜膜封好,再用锡纸将其盖上,放入冰箱避光保存。
实施例1
取一个100mL的小烧杯,称取0.128g NIPAM、0.008g PAA、0.03g SDS、0.1700gβ-CD(水相)并溶于90ml 蒸馏水中,记作水相。另取一个25mL的小烧杯,称取0.07g MAPEG、0.0197g DVB(油相)并溶于4ml二甲基亚砜(DMSO)中,记作油相。然后将水相倒入三口烧瓶中,将油相采用注射泵(3.5mL/h)逐滴滴加于水相中,同时开启超声清洗机(机械搅拌,1000rpm),滴加结束后再次超声,计时2h。然后称取1.4g分散在环己烷中的磁流体溶液(20%质量分数),将磁流体通过注射泵逐滴滴加于水相中,滴加结束后再次超声2h。提前准备一个500ml的大烧杯,底部铺满冰水混合物,将结束反应的乳液从三口烧瓶倒入小烧杯,然后将小烧杯浸入大烧杯中(保证冰水混合物能达到充分降温的目的),用泡沫将其卡死稳定,放入超声破碎机超声细乳化15min(300W),最后将破碎好的细乳化液倒回三口烧瓶中,通10min氮气并开启转头进行反应,然后将水浴锅加热到65℃,加入0.006 g KPS,再通10min氮气,时间到关闭氮气,反应过夜,第二天收样,所得的产物用M=14000的透析膜透析3天,所得样品即为磁性纳米凝胶。
量取合成好的磁性纳米凝胶溶液14ml倒入离心管,再称取0.0085g NHS倒入离心管内(摇晃一下,防止NHS沾壁),最后放置在摇床里室温下振荡25min。振荡完成后,称取0.009gEDC加入到混合液中继续振荡1.5h,得到活化液。用移液枪吸取10μl的NH2-GQDs加入到活化液中,用锡纸包裹离心管做避光处理,继续振荡11h,记为F/MNL-1。
实施例2
取一个100mL的小烧杯,称取0.129g NIPAM、0.008g PAA、0.035g SDS、0.1750gβ-CD并溶于110ml 蒸馏水中,记作水相。另取一个25mL的小烧杯,称取0.075g MAPEG、0.0199gDVB(油相)并溶于6ml二甲基亚砜(DMSO)中,记作油相。然后将水相倒入三口烧瓶中,将油相采用注射泵(3.5mL/h)逐滴滴加于水相中,同时开启超声清洗机(机械搅拌,1000 rpm),滴加结束后再次超声,计时3h。然后称取1.6g的分散在环己烷中磁流体溶液(20%质量分数),将磁流体通过注射泵逐滴滴加于水相中,滴加结束后再次超声3h。提前准备一个500ml的大烧杯,底部铺满冰水混合物,将结束反应的乳液从三口烧瓶倒入小烧杯,然后将小烧杯浸入大烧杯中(保证冰水混合物能达到充分降温的目的),用泡沫将其卡死稳定,放入超声破碎机超声细乳化25min(300W),最后将破碎好的细乳化液倒回三口烧瓶中,通20min氮气并开启转头进行反应,然后将水浴锅加热到75℃,加入0.008g KPS,再通20min氮气,时间到,关闭氮气,反应过夜,第二天收样,所得的产物用M=14000的透析膜透析3天,所得样品即为磁性纳米凝胶。
量取合成好的磁性纳米凝胶溶液16ml倒入离心管,再称取0.0087g NHS倒入离心管内(摇晃一下,防止NHS沾壁),最后放置在摇床里室温下振荡35min。振荡完成后,称取0.011gEDC加入到混合液中继续振荡2.5h,得到活化液。用移液枪吸取20μl的NH2-GQDs加入到活化液中,用锡纸包裹离心管做避光处理,继续振荡13h,记为F/MNL-2。
实施例3
取一个100mL的小烧杯,称取0.129g NIPAM、0.009g PAA、0.04g SDS、0.1750gβ-CD(水相)并溶于100ml 蒸馏水中,记作水相。另取一个25mL的小烧杯,称取0.08g MAPEG、0.0198g DVB(油相)并溶于5ml二甲基亚砜(DMSO)中,记作油相。然后将水相倒入三口烧瓶中,将油相采用注射泵(3.5mL/h)逐滴滴加于水相中,同时开启超声清洗机(机械搅拌,1000rpm),滴加结束后再次超声,计时2.5h。然后称取1.5g分散在环己烷中的磁流体溶液(20%质量分数),将磁流体通过注射泵逐滴滴加于水相中,滴加结束后再次超声2.5h。提前准备一个500ml的大烧杯,底部铺满冰水混合物,将结束反应的乳液从三口烧瓶倒入小烧杯,然后将小烧杯浸入大烧杯中(保证冰水混合物能达到充分降温的目的),用泡沫将其卡死稳定,放入超声破碎机超声细乳化20min(300W),最后将破碎好的细乳化液倒回三口烧瓶中,通15min氮气并开启转头进行反应,然后将水浴锅加热到70℃,称取0.007g KPS,并加入,再通15min氮气,时间到,关闭氮气,反应过夜,第二天收样,所得的产物用M=14000的透析膜透析3天,所得样品即为磁性纳米凝胶。
量取合成好的磁性纳米凝胶溶液15ml倒入离心管,再称取0.0086g NHS倒入离心管内(摇晃一下,防止NHS沾壁),最后放置在摇床里室温下振荡30min。振荡完成后,称取0.010gEDC加入到混合液中继续振荡2h,得到活化液。用移液枪吸取40μl的NH2-GQDs加入到活化液中,用锡纸包裹离心管做避光处理,继续振荡12h,记为F/MNL-3。
实施例4
取一个100mL的小烧杯,称取0.13g NIPAM、0.095g PAA、0.04g SDS、0.1755gβ-CD(水相)并溶于110ml 蒸馏水中。另取一个25mL的小烧杯,称取0.085g MAPEG、0.0195g DVB(油相)并溶于5.5ml二甲基亚砜(DMSO)中。然后将水相倒入三口烧瓶中,将油相采用注射泵(3.5mL/h)逐滴滴加于水相中,同时开启超声清洗机(机械搅拌,1000 rpm),滴加结束后再次超声,计时3h。然后称取1.55g分散在环己烷中的磁流体溶液(20%质量分数),将磁流体逐滴通过注射泵逐滴滴加于水相中,滴加结束后再次超声3h。提前准备一个500ml的大烧杯,底部铺满冰水混合物,将结束反应的乳液从三口烧瓶倒入小烧杯,然后将小烧杯浸入大烧杯中(保证冰水混合物能达到充分降温的目的),用泡沫将其卡死稳定,放入超声破碎机超声细乳化25min(300W),最后将破碎好的细乳化液倒回三口烧瓶中,通20min氮气并开启转头进行反应,然后将水浴锅加热到75℃,称取0.0075g KPS,并加入,再通20min氮气,时间到,关闭氮气,反应过夜,第二天收样,所得的产物用M=14000的透析膜透析3天,所得样品即为磁性纳米凝胶。
量取合成好的磁性纳米凝胶溶液16ml倒入离心管,再称取0.0086g NHS倒入离心管内(摇晃一下,防止NHS沾壁),最后放置在摇床里室温下振荡35min。振荡完成后,称取0.011gEDC加入到混合液中继续振荡2.5h,得到活化液。用移液枪吸取60μl的NH2-GQDs加入到活化液中,用锡纸包裹离心管做避光处理,继续振荡13h,记为F/MNL-4。
对制备过程中的中间产物及本发明最终产物进行性能分析。
图1分别为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的红外谱图。
图1.a为磁性纳米水凝胶的红外谱图,3390cm-1处为O-H或N-H的伸缩振动峰,2929cm-1处为C-H的伸缩振动峰,1723cm-1处为PAA中C=O伸缩振动峰,1656 cm-1处为NIPAM中的C=O伸缩振动峰,1544cm-1处为NIPAM的O-H的变形振动峰,1447cm-1处为PAA中的O-H弯曲振动峰,1373cm-1处为C-H的伸缩振动峰,1118cm-1处为C-N的伸缩振动峰,1027cm-1处为β-CD的C-O-C的特征吸收峰,579cm-1处为Fe3O4的特征吸收峰。这些特征峰表明磁性纳米水凝胶被成功制备。图1.b为荧光/磁性纳米复合凝胶的红外谱图,1723cm-1处 PAA中C=O伸缩振动峰强度变小,可能由于 NH2-GQD中的氨基和PAA中的羧基酰胺化。1710cm-1处为酰胺基中的C=O伸缩振动峰,1560cm-1处为酰胺基中N-H的变形振动峰,1462cm-1处为C-N伸缩振动峰,1215cm-1处为C-O伸缩振动峰,这些特征峰表明NH2-GQDs被成功键合在磁性纳米水凝胶上。
图2为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的粒径分析图。
由图2可知,荧光/磁性纳凝胶的平均粒径分别为97.7、98.5、102.9、105.6nm,呈逐渐增加趋势,随着NH2-GQD含量的增加,磁性纳米水凝胶表面键合的NH2-GQD增多,从而粒径变大。从图2.a、2.b、2.c、2.d中可知NH2-GQD含量为10、20、40、60μl时制备出的荧光/pH/温敏/磁性多重响应的纳米凝胶的粒径并不均一,分散性一般。当NH2-GQDs含量40μl时,荧光/磁性纳米复合凝胶分布较均匀,粒径在40-300nm。
图3为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的扫描电镜图。
由图可知,荧光/pH/温敏/磁性多重响应的纳米凝胶呈现出均一的多孔结构,这些多空结构是由于被包裹在水凝胶内部的水分子被干燥抽走后形成的。三维网状结构内壁有“褶皱”,这些“褶皱”增大了荧光/pH/温敏/磁性多重响应的纳米凝胶的比表面积。
图4为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的透射电镜图。
由图4.a和4.b可知,磁性纳米凝粒径比较均一,分布均匀,呈单分散性。由图4.c和4.d可知,荧光/pH/温敏/磁性多重响应的纳米凝胶粒径主要集中分布在60nm左右,有些粒径达到300nm,这与粒径分析相一致。对比发现,荧光/pH/温敏/磁性多重响应的纳米凝胶的粒径大于磁性纳米凝胶的粒径,因为NH2-GQDs通过氨酸络合反应键合于磁性纳米凝胶。
图5为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的温度响应性图。
由图可知,25℃至35℃时粒径随着温度的变化呈线性增长趋势,在35℃时粒径达到了最大值,35℃至42.5℃时粒径随温度的变化呈线性减小趋势。发生这种曲线变化可能是由于聚-N-异丙基丙烯酰胺(NIPAM)***的水凝胶是响应负温度刺激的纳米水凝胶,因此其体积相变温度约为35°C,而当温度超过35°C时,亲水基团具有分子链,当它被水分子破坏并与之形成氢键。结果就是水凝胶***变得更疏水,水分子被推出凝胶***,导致体积急剧减少。由此可看出制备出的荧光/pH/温敏/磁性多重响应的纳米凝胶具有一定的温度响应敏感性。
图6分别是具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的pH响应图。
由图可知,25℃下荧光/pH/温敏/磁性多重响应的纳米凝胶的平均粒径比37.5℃下的平均粒径要小,这说明纳米凝胶在不同的pH下依然有很好的温度响应性。在图6中的a曲线和b曲线都在存在着粒径从大到小,在变大的线性关系,都在pH=6时达到了最低值,这可能是由于聚丙烯酸(PAA)的酸性解离常数(Pka)大约为5.5左右,当pH<5.5时,PAA与NIPAM之间有氢键作用,这将减少纳米凝胶的吸水率并减小粒径。当pH>5.5时,羧化质子化以形成负离子,从而增加了水凝胶的吸水率并增加了粒径,证实了荧光/pH/温敏/磁性多重响应的纳米凝胶具有良好的pH响应性。
图7为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的磁响应图谱。
由图可知,剩磁和矫顽力都基本趋于0,体现了荧光/pH/温敏/磁性多重响应的纳米凝胶具有良好的超顺磁性。
图8为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的荧光光谱图。
图8.a为NH2-GQDs的荧光光谱图,激发光波长为400nm时,制得的NH2-GQDs开始发出荧光,随后荧光强度随着激发光波长增加而增大,在激发光波长为500nm时到达峰值,随后随着波长增加,荧光强度随之减弱,直至波长为670nm时,荧光消失。图8.b为荧光/pH/温敏/磁性多重响应的纳米凝胶的荧光光谱图,在入射光波长为670nm时,荧光/pH/温敏/磁性多重响应的纳米凝胶的荧光强度达到顶峰。比较可得,NH2-GQDs的荧光强度高于荧光/pH/温敏/磁性多重响应的纳米凝胶。这可能是受取代基影响,取代基对荧光强度的影响重大。-NH2、-OH等给电子基团会使荧光增强,-COOH、卤代基等吸电子基团会使荧光减弱。本专利制得的NH2-GQDs含有大量的-NH2,因此荧光强度最高。
图9为具体实施例所制备的荧光/pH/温敏/磁性多重响应的纳米凝胶的荧光光谱图。
图9.a为NH2-GQDs的在400nm激发光下的发射光谱。激发光为400nm时,NH2-GQD的发射峰在491nm处。图9.b为不同含量NH2-GQDs的荧光/pH/温敏/磁性多重响应的纳米凝胶的荧光光谱图。由图可知,荧光/pH/温敏/磁性多重响应的纳米凝胶的荧光性能与NH2-GQDs的含量成非线性关系。当NH2-GQDs含量为10-40μl逐渐增加时,荧光/pH/温敏/磁性多重响应的纳米凝胶的荧光强度也随之变大。当NH2-GQDs含量为40μl时,荧光/pH/温敏/磁性多重响应的纳米凝胶的荧光强度最强。而当NH2-GQDs含量为60μl时,荧光/pH/温敏/磁性多重响应的纳米凝胶的荧光强度最弱。这种现象发生的原因是由于NH2-GQDs的猝灭,当NH2-GQDs的浓度升高时,NH2-GQDs会发生自吸收现象,从而引发荧光猝灭。根据这种原理可知图中所反映的荧光强度的变化是符合客观规律的。
综上所述,通过利用纳米粒度仪、透射电子显微镜、荧光光谱仪等对制得的样品进行表征,表征结果如下:
(1)通过红光光谱分析表明磁性纳米水凝胶被成功制备
(1)通过ζ电位分析、粒径分析和荧光光谱分析,筛选了合成荧光/pH/温敏/磁性多重响应纳米凝胶的最优配方,加入40μl时,荧光强度最大。
(2)扫描电镜、透射电镜结果显示,荧光/pH/温敏/磁性多重响应的纳米凝胶分散均匀,形貌良好,表现初步呈现三维孔状的结构。
(3)对温度、pH响应性能分析得到荧光/pH/温敏/磁性多重响应的纳米凝胶具有一定的温度响应敏感性和良好的pH响应性。
(4)磁响应图谱显示荧光/pH/温敏/磁性多重响应的纳米凝胶具有良好的超顺磁性。
Claims (5)
1.一种荧光/pH/温敏/磁性多重响应的纳米凝胶载体的制备方法,其特征在于,包括以下步骤:
步骤1:以N-异丙基丙烯酰胺NIPAM和聚丙烯酸PAA为温度和pH响应性单体,以磁流体为磁响应性单体,二乙烯基苯DVB为交联剂,加入环糊精β-CD,通过细乳液聚合法制备出磁性纳米凝胶;
步骤2:将磁性纳米凝胶活化后,通过氨羧络合反应在磁性纳米凝胶表面键合NH2-GQDs,得到荧光/pH/温敏/磁性多重响应的纳米凝胶;
所述的步骤2,包括如下具体步骤:
A、取磁性纳米凝胶溶液14~16ml,称取0.0085~0.0087g N-羟基琥珀酰亚胺NHS,放置于25℃的全温振荡培养箱,振荡25~35min;
B、振荡结束后,称取0.009~0.011g 二亚酰胺酸盐EDC加入到混合液中继续振荡1.5~2.5h, 加入10~60μl的NH2-GQDs,避光振荡11~13h,即得荧光/pH/温敏/磁性多重响应的纳米凝胶;
所述步骤2B中,EDC为0.01g,振荡时间为2h,NH2-GQDs为40μl。
2.根据权利要求1所述的一种荧光/pH/温敏/磁性多重响应的纳米凝胶的制备方法,其特征在于:所述的步骤1,包括如下具体步骤:
A、称取0.128~0.130g NIPAM、0.008~0.010g PAA、0.03~0.05g SDS、0.1700~0.1800g β-CD并溶于90~110ml 蒸馏水中,记作水相;
称取0.07~0.09g MAPEG和0.0197~0.0199g DVB溶于4~6ml二甲基亚砜(DMSO)中,记作油相;
将油相通过注射泵逐滴滴加于水相中,同时进行超声,滴加结束后再次超声2~3h;
称取1.4~1.6g分散在环己烷中的磁流体溶液(20%质量分数),通过注射泵逐滴滴加于水相中,滴加结束后再次超声2~3h;采用超声破碎机进行细乳化15~25min,得细乳化液;
B、将细乳化液转置三口烧瓶中,通氮气10~20min,将水浴锅加热到65~75℃后加入0.006~0.008g KPS,通氮气10~20min,持续反应过夜,将制备产物用M=14000的透析袋透析3天,所得样品即为磁性纳米凝胶。
3.根据权利要求2所述的一种荧光/pH/温敏/磁性多重响应的纳米凝胶的制备方法,其特征在于:
所述步骤1A中NIPAM为0.129g, MAPEG为0.08g,DVB为0.0198g,超声时间均为2.5h,磁流体为1.5g;
注射泵的滴加速度为3.5mL/h。
4.根据权利要求1所述的一种荧光/pH/温敏/磁性多重响应的纳米凝胶的制备方法,其特征在于:
所述步骤2A中,室温下振荡时间为30min。
5.权利要求1-4任一制备方法所制备的一种荧光/pH/温敏/磁性多重响应的纳米凝胶载体。
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