CN102083741A - pH敏感性金属纳米粒子及其制造方法 - Google Patents
pH敏感性金属纳米粒子及其制造方法 Download PDFInfo
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Abstract
本发明涉及pH敏感性粒子及其制造方法和用途,具体来说,涉及pH敏感性金属纳米粒子及其制造方法,以及利用光热治疗的杀灭细胞的治疗用途。本发明的pH敏感性金属纳米粒子,在金属纳米粒子上形成了根据pH的不同电荷发生变化的pH敏感性配体化合物,因此可以在如癌细胞的具有非正常pH环境的细胞中凝聚。本发明的pH敏感性金属纳米粒子在凝聚后可以通过光热过程诱导杀灭细胞,所以可以进行如癌细胞治疗的利用杀灭细胞的治疗。
Description
技术领域
本发明涉及pH敏感性粒子及其制造方法和用途,具体来说,涉及pH敏感性金属纳米粒子及其制造方法和利用光热治疗的杀灭细胞的治疗用途。
背景技术
如癌细胞的非正常细胞的周边环境,与显示出pH7.2~7.4的体内环境不同,为pH6.0至7.2的弱酸性。正在研究利用这样的癌细胞的特性,治疗癌症的方法。
成均馆大学校产学协力团享有的韩国专利第802080号中如下的方法,即,由具有pH敏感性的生物分解性聚(β-氨酯)化合物和亲水性聚乙烯醇类化合物共聚而形成共聚物,由此利用自体内持有的双亲性和根据pH不同而变化的离子化特性形成胶束结构,并通过该胶束结构利用pH变化的目标指向,向癌细胞传递药物,从而杀灭癌细胞。
在WO2002/20510号中记载了包括酸敏感性的环正酯以及一种以上亲水性取代体的酸敏感性化合物及其盐。该化合物与治疗性分子形成接合体(脂质体、复合物、纳米粒子等)后,向pH为酸性的细胞组织或区域放出治疗性分子。
金属纳米粒子由于其特有的表面等离子性具有独特的光学性质。表面等离子性是指在作为导体的金属纳米粒子表面和空气、水等电介质之间入射光时,由于与光所具有特定能量的电磁场的共振,金属表面的电子集中振动的现象。这样的光和金属纳米粒子的相互作用很强,所以与通常的有机颜料相比,在共振波长下的吸光系数大。另外,根据粒子的大小、形态、所分散的溶剂等的不同,共振波长也不同,正在进行制造具有多种大小、形态、表面特性的金属纳米粒子,应用于光学传感器或聚光装置。
最近,作为生物学上的引用,利用金纳米粒子的聚光效果的光热治疗的可能性受到了关注。光热治疗师将光能转化为热能而攻击癌细胞的方法。在金纳米粒子的表面聚光的光会通过多种路径放出,其中,电子-点阵振动、电子-电子散射等是伴随热的放出过程。此时,局部放出的热能,由于金纳米粒子的突出的聚光效果和大的体表面积,对于杀灭细胞来说是充分的能力。另外,通常癌细胞与正常细胞相比耐热性弱,所以通过调整在金纳米粒子中聚光的光量,控制局部的热量,可以在不损伤正常细胞的情况下选择性地杀灭癌细胞。
在韩国2006年专利申请第102604号中公开的粒子,在50~500nm大小的二氧化硅粒子上形成包含磁体粒子的金涂布层,形成了癌细胞目标指向型配体。癌细胞目标指向型配体与癌细胞结合,可以诊断癌症或利用磁体的磁性得到磁共振图像,而且放射出近红外线区域的电磁波脉冲,利用吸收能量的金纳米外壳放出的热,选择性地杀灭癌细胞。这种方式存在需要开发能够识别特定癌细胞的有效的生物配体,并将其与金属接合的问题。
如上所述,正持续研究能够选择性地识别多余多种癌细胞的金属纳米粒子。
发明内容
本发明的目的在于提供一种新的pH敏感性粒子。
本发明的其他目的在于提供一种pH敏感性金属纳米粒子。
本发明的其他目的在于提供一种pH敏感性纳米粒子的制造方法。
本发明的其他目的在于提供利用pH敏感性金属纳米粒子杀灭非正常细胞的方法。
本发明的其他目的在于提供一种新的pH敏感性化合物。
本发明的其他目的在于提供一种新的pH敏感性化合物的合成方法。
本发明的其他目的在于提供一种pH敏感性粒子作为传感器的用途。
为了达到上述目的,本发明的pH敏感性纳米粒子,其特征在于,在表面形成根据pH的不同电荷发生变化的化合物。
在本发明中,上述金属纳米粒子可以是在如金属粒子或二氧化硅等的物质上涂布金属的粒子。上述金属可以是单一金属或合金,也可以附着根据pH的不同电荷发生变化的化合物,优选为金粒子。
在本发明中,上述金属纳米粒子的表面所形成的化合物具有根据pH的不同而化合物的电荷发生变化的结构,可以以配体形态与在金属粒子表面露出的金属原子结合。
在本发明中,上述化合物优选是以pH7.0为基准化合物的电荷发生变化的化合物。在本发明的一实施例中,上述化合物在pH从碱性或中性变化为酸性时从负电荷变为正电荷。
在本发明中,上述化合物可以由下述化学式(I)表示、
另外,本发明的制造pH敏感性金属纳米粒子的方法,是在金属纳米粒子的表面附着根据pH的不同电荷发生变化的化合物。
在本发明中,上述金属纳米粒子可以采用可以附着根据pH的不同电荷发生变化的化合物的多种产品,在本发明的一实施例中,上述金属粒子是包含于化合物的硫原子可以结合的金粒子或金涂布粒子。在本发明的优选实施例中,根据pH的不同电荷发生变化的化合物,可以有如下化学式(I)表示。
在本发明中,上述根据pH的不同电荷发生变化的化合物,可以以取代附着在金属纳米粒子的表面的另一化合物,例如,为了使金属纳米粒子稳定而附着在表面的柠檬酸盐的方式附着。
另外,本发明的光热治疗方法,其特征在于,投入pH敏感性金属纳米粒子而使其凝聚,并在凝聚的金属纳米粒子上照射光,由此杀灭非正常细胞。
在本发明中,上述非正常细胞是显示非正常的pH环境的细胞,例如,是显示酸性pH环境的癌细胞。
在本发明中,pH敏感性金属纳米粒子,优选使用可以接受从细胞外部照射的光并通过光热作用杀灭细胞的金属。可以适用在光热治疗中使用的通常的细胞,优选金粒子。
在本发明中,上述金属纳米粒子优选具有可以渗透到细胞中的大小。在本发明的实施例中,上述金属纳米粒子的直径为20nm以下,更加优选具有5~15nm程度的大小。
在本发明中,上述金属纳米粒子接近和/或渗透到非正常细胞,在酸性pH环境中凝聚,并且在抑制向细胞外部排出的状态下进行光热治疗,由此杀灭细胞。
在本发明中,上述金属纳米粒子是可以检测如癌细胞的非正常细胞的低的pH而凝聚的pH敏感性粒子。
在本发明的实施例中,上述金属纳米粒子可以是在表面附着有可酸性pH环境中凝聚的化合物的形态。
在本发明的实施例中,金属纳米粒子,在粒子环境从碱性pH变为酸性pH时,在表面形成的化合物经过水解反应等反应,由此电荷发生变化。如果化合物的电荷发生变化,理论上并没有现定于此,但在电荷发生变化的过程中,粒子由于静电引力而相互凝聚。
令人惊讶的是,上述pH敏感性金属纳米粒子在凝聚的同时吸光波长变大。在利用透射力强的近红外线等长波长的光时,不仅可以加热在皮肤或皮下附近凝聚的金属纳米粒子,而且还可以加热在身体或内脏内部凝聚的金属纳米粒子。因此,可以与癌细胞的发生部位无关地进行光热治疗,从而大幅度扩展了光热治疗的范围。
本发明由具有如下化学式(I)结构的pH敏感性化合物构成。
另外,在本发明的pH敏感性金属纳米粒子的制造方法,包括如下步骤:
使硫辛酸和乙二胺发生反应而制造具有下述化学式(II)所示结构的化合物的步骤;
使上述化学式(II)所示化合物与柠康酐反应,制造下述化学式III所示化合物的步骤;
使上述化学式(III)所示化合物与硼氢化钠反应,制造下述化学式(I)所示化合物的步骤。
本发明的pH敏感性粒子,仅在如癌细胞的非正常pH的细胞中凝聚,并吸收长波长的光,因此,可以利用这一点在多种用途中使用。例如,本发明的pH敏感性粒子,可以作为癌症诊断用药、造影剂、癌症治疗剂、光敏剂等用途使用。另外,在将pH敏感性纳米粒子附着于传感器的表面使用时,可以作为测定pH变化的传感器使用。
另外,本发明提供吸收红外线的5~20nm的金纳米粒子凝聚而成的凝聚体。上述凝聚体为束(cluster)状态,上述束的直径为0.1~10微米,优选为1~3微米。
另外,本发明涉及利用凝聚的金纳米粒子吸收红外线而使其发热的方法。
本发明的pH敏感性金纳米粒子,在中性或碱性条件下分散均匀,且仅吸收600nm以下的波长带。但是,在酸性条件下,纳米粒子的表面电荷发生变化,在此过程中由于静电引力,相邻的纳米粒子之间产生凝聚。由此形成的纳米粒子凝聚体,由于表面等离子性的特性,其吸光带转为600nm以上的可见光线长波长带和红外线带。
在本发明的实施例中,在引导杀灭癌细胞的光热治疗中应用的情况下,若将pH敏感性金纳米粒子投入到癌组织中,则由于癌组织的特殊的酸性环境,在癌组织的特定位置形成凝聚体。另外,导入到癌细胞内部的纳米粒子被引导成在如核内体(endosome)的细胞内具有酸性pH的部分急剧形成凝聚体。由于在细胞内形成凝聚体,抑制了胞泌作用,抑制了导入到癌细胞内部的pH敏感性金纳米粒子的排出,从而可以期待抗癌疗法的效率的提高。利用pH敏感性金纳米粒子的癌症光热治疗的最大的优点在于,pH敏感性金纳米粒子被引导到癌组织内癌细胞而形成凝聚体,该凝聚体的吸光波长带由于其表面等离子性的特性转为长波长带。因此,组织透过率优良,可以使用能应用于距离皮肤较深存在的癌组织的长波长光源。现有的利用光的抗癌疗法的缺点在于光敏剂所发硬的波长带较窄,因此被限制于在如皮肤癌的不需要特别的组织透过率的癌症的治疗用途。因此,利用本发明的pH敏感性金纳米粒子可以克服这样的缺点。另外,仅由形成凝聚体的pH敏感性金纳米粒子吸收来自长波长光源的能量,所以可以更具有选择性地破坏癌细胞。现有的利用光的抗癌疗法中的光敏剂,不会因为周围环境而改变吸光带,所以不能显示出与本发明粒子相同的选择性。
另外,本发明提供具有1~500nm的平均直径、含有pH敏感性化合物的、在酸性pH下凝聚为特征的金属纳米粒子。
在本发明中,上述pH敏感性化合物可以适用公知的pH敏感性高分子和/或低分子化合物,上述化合物额可以通过公知的方式导入到金属粒子中,例如喷涂等涂布、配体取代等取代、金属粉末与化合物粉末的混合等混合,只要导入pH敏感性化合物而在酸性pH下使金属粒子凝聚,则可以没有其他限制地适用。
发明效果
根据本发明提供pH敏感性金属纳米粒子及其制造方法。本发明的pH敏感性粒子可以在具有非正常pH的细胞中凝聚,由此可以提供到治疗剂、诊断剂等多种用途。
附图说明
图1是本发明的pH敏感性金纳米粒子的透射电镜照片。(从左上侧按照顺时针方向为)在pH7.3水溶液状态下分散的pH敏感性金纳米粒子、在pH5.5水溶液状态下分散后分别经过10分钟、30分钟、120分钟、90分钟、60分钟的pH敏感性金纳米粒子(大小条形,在pH7.3下为50nm,在pH5.5下为500nm)。
图2是本发明pH敏感性金纳米粒子根据pH以及时间的pH敏感性金纳米粒子的吸光光谱。黑色是pH7.3条件下分散后经过24小时后测定吸光光谱的结果,青色、绿色和红色是在pH5.5下分散到醋酸缓冲溶液后分别经过10分钟、30分钟、90分钟后测定的吸光光谱。
图3是使本发明的pH敏感性金纳米粒子捕获至宫颈癌细胞后观察的暗场显微镜照片。由于在细胞内形成凝聚体的金纳米粒子,显示为红色。
图4是与本发明的pH敏感性金纳米粒子一起培养的宫颈癌细胞实验群(左侧列)和比较群(右侧列)的光学显微镜照片。利用发出660nm波长的光的激光照射10分钟,之后染色为台盼蓝(Trypan blue)而进行观察的光学显微镜照片。从上到下份使用了140mW、85mW、以及55mW的激光功率。由于pH敏感性金纳米粒子的光热效果被杀灭的细胞因染色法而显示成青色。
具体实施方式
实施例
将柠康酸(Lipoic acid)(1)溶解到无水氯仿(anhydrouschloroform)后,在真空环境下添加1.3当量的羰基二咪唑(carbonyldiimidazole)并搅拌5分钟,分离除了剩余羰基二咪唑的反应溶液层。将相当于柠康酸的5当量的乙二胺(ethylene diamine)在氮气环境下溶解到无水氯仿中后,在冰浴(ice bath)中降低温度的状态下添加上述溶液并搅拌1小时(所得物质为(2))。将反应溶液用10% NaCl水溶液萃取3次、用三次蒸馏水萃取1次而进行提纯,添加柠康酐(citraconic anhydride)并在常温下搅拌24小时之后,过滤生成的固体(所测物质为(3))。将该固体溶解于用2N NaOH使pH调整为9的水溶液之后,添加1当量的NaBH4并在常温下搅拌4小时。合成的pH敏感性配体(4),未经精制过程,直接使用。
制造的化合物(4)在酸性条件下水解(hydrolysis)而氨分解,通过下属途径生成伯胺和柠康酸,生成的伯胺在酸性条件下带正电荷。
用柠檬酸盐稳定化的金纳米粒子的合成
将金的球体的HAuCl4溶解到蒸馏水中并在120℃下搅拌加热30分钟,之后添加柠檬酸三钠(trisodium citrate),接着在120℃下加热搅拌2小时。此时,柠檬酸三钠发挥还原剂以及表面配体的作用,在数分钟内溶液的颜色从黄色转变为红色,由此可以确认形成了金纳米粒子。之后,在常温下搅拌冷却(Ind.Eng.Chem.Res.2007,56,3128-3136)。
pH敏感性金纳米粒子的合成
在过量溶解有所合成的pH敏感性配体的水溶液中,添加用柠檬酸盐(citrate)稳定化的金纳米粒子,在常温下搅拌8小时。pH敏感性配体的一侧作用基团为二硫酚(dithiol),与作用基团为羧酸(carboxylicacid)的柠檬酸盐相比,与金纳米粒子具有强的表面结合力,因此柠檬酸盐被配体交换为pH敏感性配体。之后进行透析,去除多余的配体。
pH敏感性金纳米粒子的凝聚特性确认
将pH敏感性金纳米粒子分别分散到pH7.3的水溶液和pH5.5的水溶液中,并且从分散后经过10分钟、30分钟、120分钟、90分钟、60分钟之后利用投射电镜观测pH敏感性金纳米粒子是否凝聚。结果示于图1。如图1所示,观察到了在pH5.5酸性条件下形成凝聚体的情况。pH敏感性金纳米粒子在pH7.3的条件下与经过时间无关地以平均15nm大小的纳米粒子均匀分散。将这样的pH敏感性金纳米粒子水溶液变换为pH5.5的条件,则随着时间的推移,形成凝聚体,且该凝聚体的大小逐渐变大为数微米。
金纳米粒子的凝聚带来的吸光特性
将合成的pH敏感性金纳米粒子暴露在与正常细胞类似的pH7.3的环境和雨癌细胞周围类似的pH5.5的环境中,之后按照经过实践测定了吸收光谱。在pH7.3的条件下分散后经过24小时时测定了吸光光谱,在pH5.5的醋酸缓冲溶液中分散后分别经过10分钟、30分钟、90分钟时测定了吸光光谱,结果示于图2。
pH敏感性金纳米粒子通常在生物学环境的pH7.3下只强烈吸收600nm以下的可见光区域的光,但pH调整为5.5时,随着时间的推移,吸收波长逐渐变为长波长,能够吸收红色-近红外线区域的光。这是因为,产生了pH敏感性金纳米粒子表面的配体的水解,从负电荷转变为正电荷的过程中,粒子由于静电引力相互结合而形成凝聚体的缘故。
正常细胞具有pH7.3~7.4程度的中性环境,正常细胞周围的pH敏感性金纳米粒子只吸收600nm以下的可见光区域的光。但是,pH5.5左右的酸性环境的癌细胞周围的pH敏感性金纳米粒子,则形成凝聚体,由此能够吸收红色-红外线区域的光。红色-红外线区域的光,在针对癌细胞的选择性的光热治疗中,皮肤和血液等生物体物质的吸收、散射的程度较小,体内透射性高,因此具有可以提高光热效果的优点。
利用暗场显微镜的观测
对于宫颈癌细胞进行pH敏感性金纳米粒子的处理之后,用暗场显微镜进行拍照。所拍下的照片示于图3。形成凝聚体,吸收波长向长波长移动,吸收红色-近红外线区域的光,因此,在暗场显微镜中显示为红色。
PH敏感性金纳米粒子通过内包作用堆积到核内体而移入细胞内,则在核内体变为溶酶体(lysosome)的过程中被暴露于酸性环境,因此,pH敏感性金纳米粒子形成凝聚体。
光热治疗实验
在体外(in vitro)条件下进行了pH敏感性金纳米粒子的癌光热治疗实验。实验群,将宫颈癌细胞和pH敏感性金纳米粒子一起培养而在癌细胞内诱导捕获pH敏感性金纳米粒子。比较群是在培养时没有添加pH敏感性金纳米粒子的样品。对于实验群和比较群的样品,利用发射660nm波长的光的激光照射10分钟分别为140mW、85mW和55mW的不同工序的能量。照射激光后,利用台盼蓝(Trypan blue)溶液进行染色,并用光学显微镜观察。拍摄的照片示于图4。照射激光的部分,在图中用圆圈表示。
台盼蓝染色法,选择性地仅将死细胞染色为青色。在以阈值激光功率以下的55mW激光功率照射实验群和比较群样品的情况下,两者均没有发现死细胞。这说明在光照射阈值以下的条件下pH敏感性金纳米粒子没有显示毒性。即,表示pH敏感性金纳米粒子具备作为抗癌治疗用光敏剂的要素的癌条件的非毒性特性。在利用85mW功率的激光照射光的情况下,仅在实验群的样品中出现了细胞杀灭。在利用140mW功率照射光的情况下,与利用85mW功率照射光的情况下相比,出现了更多的细胞杀灭。这说明出现了与光功率成反比地诱导杀灭细胞的光热治疗反应,也意味着pH敏感性金纳米粒子在癌症的光热治疗中是有效的。
Claims (41)
1.一种金属纳米粒子,其特征在于,在表面形成有根据pH的不同电荷发生变化的化合物。
2.如权利要求1所述的金属纳米粒子,其特征在于,所述金属纳米粒子是金属粒子或金属涂布粒子。
3.如权利要求1或2所述的金属纳米粒子,其特征在于,所述金属为金。
4.如权利要求1或2所述的金属纳米粒子,其特征在于,所述化合物在中性和碱性条件下为负电荷,在酸性环境下变为正电荷。
5.如权利要求4所述的金属纳米粒子,其特征在于,所述化合物由于水解而电荷发生变化。
7.如权利要求1或2所述的金属纳米粒子,其特征在于,所述金属纳米粒子利用电荷变化凝聚。
8.如权利要求1或2所述的金属纳米粒子,其特征在于,所述金属纳米粒子,根据凝聚度,吸光波长变长。
9.如权利要求1或2所述的金属纳米粒子,其特征在于,所述化合物作为金属的配体结合。
10.一种pH敏感性金属纳米粒子的制造方法,在金属纳米粒子的表面附着根据pH的不同电荷发生变化的化合物。
11.如权利要求10所述的方法,其特征在于,所述金属纳米粒子是金属粒子或金属涂布粒子。
13.如权利要求12所述的方法,其特征在于,所述化合物被配体取代到金属粒子中。
14.如权利要求13所述的方法,其特征在于,所述金属纳米粒子的表面用柠檬酸盐稳定化。
15.一种杀灭非正常细胞的方法,其特征在于,投入pH敏感性金属纳米粒子并使其凝聚,向凝聚的金属纳米粒子照射光。
16.如权利要求15所述的方法,其特征在于,所述非正常细胞显示酸性pH。
17.如权利要求15或16所述的方法,其特征在于,所述非正常细胞为癌细胞。
18.如权利要求15或16所述的方法,其特征在于,所述金属纳米粒子被导入到细胞内而凝聚。
19.如权利要求15或16所述的方法,其特征在于,所述金属纳米粒子是金属粒子或金属涂布粒子。
20.如权利要求15或16所述的方法,其特征在于,所述化合物在酸性pH下至少一部分电荷变化。
21.如权利要求15或16所述的方法,其特征在于,所述化合物由于水解而电荷发生变化。
22.如权利要求15或16所述的方法,其特征在于,所述化合物在酸性pH下由于配体的水解而从负电荷转变为正电荷。
24.如权利要求15或16所述的金属纳米粒子,其特征在于,所述金属纳米粒子的平均直径为20nm以下。
25.如权利要求15或16所述的金属纳米粒子,其特征在于,所述光为红色光或红外线。
26.如权利要求25所述的方法,其特征在于,所述光为激光。
29.一种传感器,包括权利要求1~9中任一项所述的pH敏感性粒子。
30.一种癌症诊断方法,其特征在于,投入权利要求1~9中任一项所述的粒子,拍摄暗场显微镜照片,由此诊断癌症。
31.一种造影剂,包括权利要求1~9中任一项所述的pH敏感性粒子。
32.一种癌症诊断剂,包括权利要求1~9中任一项所述的pH敏感性粒子。
33.一种癌症治疗剂,包括权利要求1~8中任一项所述的pH敏感性粒子。
34.一种粒子发热方法,使凝聚的金纳米粒子吸收红外线而使其发热。
35.如权利要求34所述的粒子发热方法,其特征在于,所述金纳米粒子具有20纳米以下的平均直径。
36.一种平均直径为0.5~2微米的金属纳米粒子束,由平均直径为20纳米以下的金属纳米粒子组成。
37.如权利要求36所述的金属纳米粒子束,所述束吸收紫外线。
38.一种金属纳米粒子,其特征在于,具有1~50纳米的平均直径,含有pH敏感性化合物,在酸性pH下凝聚。
39.如权利要求38所述的金属纳米粒子,其特征在于,所述pH敏感性化合物是pH敏感性高分子和/或低分子化合物。
40.如权利要求38或39所述的金属纳米粒子,其特征在于,所述化合物通过涂布、取代或混合的方式导入到金属粒子。
41.一种化合物,用下述化学式(III)表示,
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Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1340527C (en) * | 1988-05-31 | 1999-05-04 | Lidia Vallarino | Macrocyclic complexes of yttrium, the lanthanides and the actinides having peripheral coupling functionalities |
US6530944B2 (en) * | 2000-02-08 | 2003-03-11 | Rice University | Optically-active nanoparticles for use in therapeutic and diagnostic methods |
DE60115667T2 (de) | 2000-09-05 | 2006-08-24 | Centelion | Säureempfindliche verbindungen, deren herstellung und verwendungen |
GB0321937D0 (en) * | 2003-09-19 | 2003-10-22 | Univ Liverpool | Nanoparticle conjugates and method of production thereof |
US7601331B2 (en) * | 2004-11-10 | 2009-10-13 | National University Of Singapore | NIR-sensitive nanoparticle |
KR100645597B1 (ko) | 2005-03-24 | 2006-11-14 | 이지로보틱스 주식회사 | 로봇 리모컨 서비스 방법 및 장치 |
KR100713745B1 (ko) | 2006-02-27 | 2007-05-07 | 연세대학교 산학협력단 | 상전이 리간드로 코팅된 수용성 자성 또는 금속 산화물나노입자 및 이의 제조방법 |
KR20080008668A (ko) * | 2006-07-20 | 2008-01-24 | 재단법인서울대학교산학협력재단 | 자성체 나노입자를 이용하여 단백질을 선택적으로 결합,분리 또는 정제하는 방법 |
KR100802080B1 (ko) | 2007-03-28 | 2008-02-11 | 성균관대학교산학협력단 | pH 민감성 블록 공중합체 및 이를 이용한 고분자 마이셀 |
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CN102989016A (zh) * | 2012-11-05 | 2013-03-27 | 浙江大学 | 一种具有pH敏感性的纳米微粒材料及其制备方法 |
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CN113899732A (zh) * | 2021-09-30 | 2022-01-07 | 长沙新材料产业研究院有限公司 | pH值敏感型配体修饰纳米金及其制备方法 |
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