CN108671230A - 一种金纳米壳磁性plga微胶囊及其制备方法 - Google Patents
一种金纳米壳磁性plga微胶囊及其制备方法 Download PDFInfo
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Abstract
一种金纳米壳磁性PLGA微胶囊的制备方法,选用PLGA高分子微胶囊作为载体,双乳化法装载Fe3O4和(NH4)2CO3,静电吸附将金纳米粒组装于胶囊表面。通过冷冻干燥将(NH4)2CO3水相升华形成微小空穴,使得微胶囊在超声波扫描下可以产生对比增强信号,实现超声造影;装载MRI造影剂(Fe3O4)获得人体的三维结构图像,显示出发生组织病变前的功能代谢情况,实现早期诊断;并通过表面引晶技术原位形成金纳米壳层,使得在近红外光照射下产热杀伤肿瘤细胞,实现集肿瘤成像和光热治疗于一体的多功能作用。它可以将疾病的诊断和治疗这两个相对独立的过程整合起来以减小两次注射药物所带来的副作用给患者的痛苦和风险。
Description
技术领域
本发明属于高分子功能材料制备领域,具体涉及一种用于MRI/超声双模式成像和近红外诊疗一体化的金纳米壳磁性PLGA微胶囊的制备方法。
背景技术
在肿瘤的治疗中,虽然手术、化疗或放疗已经取得了很大的进展,但是这些治疗方式都会对患者带来副作用,造成极大负担,并且在癌症发生恶性转移后,无论是何种方式都是很难彻底治愈。所以寻找和开发癌症的新型疗法是生物医学研究中的焦点。
从发现疾病到恢复健康,一般需要经过诊断和治疗两个阶段。疾病的诊断是一个多种方式综合使用的复杂过程,诊断结果是否快速准确直接决定着治疗是否及时有效。以医学研究和临床诊断为目标的医学成像,由于不同成像手段的实现原理各不相同,使得他们各自具有不同的优势和缺点。
无创性或者低创伤性治疗-热疗,能利用外界物理能量将肿瘤区域加热至有效治疗温度,改变肿瘤细胞所处环境,利用正常组织可以通过血管扩张和血流加速来进行散热,使其与肿瘤组织对温度能耐受力的差异,致使肿瘤细胞变性坏死,从而达到治疗效果,是一种非侵入性的治疗方法。有效的光热疗法需要光热剂的辅助,光热剂一般需要有良好的光热转换效率,无毒,易于修饰功能基团等优点。目前,金纳米材料作为无机光热治疗剂,因其良好的生物相容性、优异的光学、光热转换效率高而被广泛应用于生物医学研究,如金纳米粒、金纳米棒、金纳米壳、金纳米笼等。金纳米材料可以通过外界近红外激光产生热效应,通过高温杀伤癌细胞,实现肿瘤的光热治疗。此外,调节高分子聚合物形成的介电核心与表面金纳米壳两者比例,来调控金纳米壳层的表面等离子共振光谱,使其覆盖近红外区域,成为一种有效的光吸收剂来实现了肿瘤的光热消融治疗。
人体内不同物质、组织或器官彼此之间所含的氢原子核(即质子)密度皆不相同,通过MRI 成像可以得到不同组织或器官中氢原子核的磁共振信号强度及磁共振弛豫时间,包含了很多体内组织的生化信息。因此MRI造影剂可以显示或监测发生组织病变前的功能代谢情况,已成为疾病尤其是癌症的一种有效的早期诊断方法。 超顺磁性造影剂是一种阴性MRI 造影剂,由外部稳定包裹材料与纳米氧化铁晶体核(Fe3O4)组成,又称为T2型造影剂,通过缩短质子的T2 弛豫时间,从而降低含造影剂部位在 T2加权磁共振图像上信号强度。
为了实现诊断和治疗一体化,使病人在得到全面准确的诊断结果之后,就能根据需要对症下药,进行有针对性的治疗,减小两次注射药物所带来的副作用给患者的痛苦和风险。而将疾病的诊断和治疗在传统的临床应用中的两个相对独立的过程整合起来的一种全新的医疗处理方式逐渐发展起来。因此本研究选用聚乳酸-羟基乙酸共聚物(PLGA)为成膜材料,内载氧化铁纳米粒子(Fe3O4)和易升华的(NH4)2CO3,外包覆金纳米壳层并通过共价结合修饰PEG,提高微胶囊的分散性和稳定性,同时使其具有良好的生物相容性。此外装载的Fe3O4具有磁共振成像,对人体组织做出形态与功能两方面的诊断评价;通过冷冻干燥将(NH4)2CO3水相升华形成微小空穴,使得微胶囊在超声波扫描下可以产生对比增强信号,实现超声造影;同时包裹的金纳米壳层能在近红外激光照射下产生的热能有效杀伤肿瘤细胞组织。这为同时具备MRI/超声双模式成像和光热治疗效果的多功能微胶囊为疗诊一体化技术在的临床上的潜在应用奠定了一定的基础。
发明内容
本发明的目的在于提供一种具有MRI/超声双模式成像和光热治疗效果的多功能微胶囊用于肿瘤诊断与治疗一体化的技术。根据获得人体精准的三维结构图像进行疾病的成像诊断,并通过近红外激光照射而进行的光热治疗,极大的缩短了两次医疗过程间隔时间和减轻了两次注射药物给病人带来的副作用。将诊断和治疗两个过程合二为一,在得到诊断结果的同时,立即基于诊断结果进行对症治疗。采用超声-乳匀法,选用PLGA为成膜材料,内载Fe3O4和易升华的(NH4)2CO3,外包覆金纳米壳层,制备得到具有MRI/超声双模式成像和光热治疗效果的金纳米壳磁性PLGA微胶囊。
为实现上述目的,本发明采用如下技术方案:
采用超声-乳匀制备技术,以PLGA为成膜材料,Fe3O4为MRI造影剂,金纳米壳层为光吸收剂,制备一种多功能金纳米壳磁性PLGA微胶囊用于诊断和治疗肿瘤的高分子载体材料。
一种用于诊断和治疗肿瘤的金纳米壳磁性PLGA微胶囊的制备方法,包括以下步骤:
(1)将100 mL含10.82 g FeCl3·6H2O(0.04 mol)、3.98 g FeCl2·4H2O(0.02 mol)的水溶液置于三口烧瓶中,通氮气,机械搅拌(3000 rpm)半小时后,缓慢滴加10 mol/L的NaOH溶液50 mL。在常温下搅拌1 h,再升温至90℃,保温2 h。再逐滴加入 10 mL 油酸,继续反应30 min。待反应结束之后将体系冷却至室温,用磁铁吸引将产物分离,加入大量丙酮沉淀,磁分离,再分散在20 mL水中,加热至50℃,使丙酮挥发,并用去离子水和乙醇分别洗涤三次,40℃真空干燥,即得油酸修饰的Fe3O4纳米颗粒;
(2)取100-1000 mg的聚乳酸羟基乙酸(PLGA)和30-600 mg 油酸修饰的Fe3O4纳米颗粒分散在3-20 mL二氯甲烷中,充分溶解,作为有机相溶液A;
(3)将新配制的 0.5-10 mL 浓度为 4wt%的(NH4)2CO3水溶液作为内水相,加入有机相溶液A中形成乳液B;
(4)将乳液B逐滴地加到20-200 mL预冷的聚乙烯醇(PVA)外水相溶液中,冰水浴条件下用超声波细胞破碎仪进行乳化,形成复乳液C后,在通风橱中使二氯甲烷尽量自然挥发,然后磁吸附沉淀洗涤后即得包覆Fe3O4的PLGA微米颗粒(Fe3O4@PLGA);
(5)取80-1000 mg Fe3O4@PLGA微米颗粒悬浮在6-200 mL 浓度为1 mg/mL的聚烯丙基胺盐酸盐(PAH)溶液中,混合均匀,磁吸附沉淀以去除剩余未吸附的PAH,沉淀即为PAH 包覆的Fe3O4@PLGA微米颗粒;
(6)取氯金酸和柠檬酸钠的混合溶液100-500 mL,其中氯金酸的浓度为10 mM,柠檬酸钠的浓度为5wt%,加入 1-5 mL含0.375wt%硼氢化钠(NaBH4)的柠檬酸钠溶液后,剧烈搅拌1min,即得到柠檬酸根稳定的金纳米粒子水溶液;
(7)将(5)制备的颗粒分散于(6)所得溶液中,充分混合吸附30 min后,磁分离,弃上清液后,加入20-200 mL 浓度为2 mM 的HAuCl4水溶液中混匀,再逐滴加入新配制的1-80 mL浓度为200 mM的盐酸羟胺水溶液,搅拌反应 30 min,然后磁分离并弃去上层清液,即可得到金纳米壳磁性PLGA微胶囊(Fe3O4@PLGA@Au);
(8)将Fe3O4@PLGA@Au悬液加入新配制的 8-100 mL 浓度为 0.01 mg/mL 的mPEG4000-SH水溶液中,搅拌反应 1 h,之后使用磁分离,去离子水洗涤两次,重新悬浮后转入冻干瓶,加液氮预冷,使用冻干机在-90℃下真空干燥 3 d,即可得到表面PEG修饰的金纳米壳磁性PLGA微胶囊(Fe3O4@PLGA@Au-PEG)。
步骤(5)利用聚电解质逐层沉积的原理,使用聚阳离子电解质,通过静电吸附的方法将带正电的聚电解质PAH 吸附于PLGA表面;
步骤(7)在聚电解质 PAH 的帮助下,在其表面静电吸附金纳米粒子,再利用表面原位引晶技术,形成金纳米壳层;
步骤(8)使用冷冻干燥法除去微囊中的水相,使微囊内部形成微小空穴;使用巯基修饰的PEG与表面Au共价结合;
通过双乳化-溶剂挥发法和交替的电位变化,来包覆Fe3O4和吸附金纳米粒,制得金纳米壳磁性PLGA微胶囊。
本发明的显著优点在于:一种用于诊断和治疗肿瘤的金纳米壳磁性PLGA微胶囊,选用的PLGA材料具有良好成膜性,体内可降解和良好的生物相容性的特点,同时装载MRI造影剂(Fe3O4)和易升华的水相(NH4)2CO3,使用静电吸附将光吸收剂金纳米组装于胶囊表面,可以实现MRI/超声双模式成像和光热治疗效果的高分子功能载体。双模式成像获得人体的三维结构图像,显示出发生组织病变前的功能代谢情况,实现早期诊断;近红外光照射下产热杀伤肿瘤细胞,实现集肿瘤成像和光热治疗于一体的多功能作用。并将疾病的诊断和治疗这两个相对独立的过程整合起来以减轻给患者带来的痛苦和风险。此外,表面共价修饰PEG可以提高微胶囊的分散性和稳定性,阻止其发生聚集。
具体实施方式
实施例1
(1)将100 mL含10.82 g FeCl3·6H2O(0.04 mol)、3.98 g FeCl2·4H2O(0.02 mol)的水溶液置于三口烧瓶中,通氮气,机械搅拌(3000 rpm)半小时后,缓慢滴加10 mol/L的NaOH溶液50 mL。在常温下搅拌1 h,再升温至90℃,保温2 h。再逐滴加入 10 mL 油酸,继续反应30 min。待反应结束之后将体系冷却至室温,用磁铁吸引将产物分离,加入大量丙酮沉淀,磁分离,再分散在20 mL水中,加热至50℃,使丙酮挥发,并用去离子水和乙醇分别洗涤三次,40℃真空干燥,即得油酸修饰的Fe3O4纳米颗粒;
(2)取100 mg的聚乳酸羟基乙酸(PLGA)和50 mg 油酸修饰的Fe3O4纳米颗粒分散在二氯甲烷中,充分溶解,作为有机相溶液A;
(3)将新配制的 0.5 mL 浓度为 4wt%的(NH4)2CO3水溶液作为内水相,加入有机相溶液A中形成乳液B;
(4)将乳液B逐滴地加到20 mL预冷的聚乙烯醇(PVA)外水相溶液中,冰水浴条件下用超声波细胞破碎仪进行乳化,形成复乳液C。将复乳液C在通风橱中挥发,使有机溶剂二氯甲烷尽量自然挥发,然后磁吸附沉淀即为包覆Fe3O4的PLGA微米颗粒(Fe3O4@PLGA);
(5)取制好的80 mg Fe3O4@PLGA微米颗粒悬浮在8 mL 浓度为1 mg/mL的聚烯丙基胺盐酸盐(PAH)溶液中,混合均匀,磁吸附沉淀以去除剩余未吸附的PAH,沉淀即为PAH 包覆的Fe3O4@PLGA微米颗粒;
(6)取氯金酸和柠檬酸钠的混合溶液 100 mL,其中氯金酸的浓度为10 mM,柠檬酸钠的浓度为5wt%,加入1 mL含0.375wt%硼氢化钠(NaBH4)的柠檬酸钠溶液后,剧烈搅拌1 min,即得到柠檬酸根稳定的金纳米粒子水溶液;
(7)将(5)制备的颗粒分散于(6)所得溶液中,充分混合吸附30 min后,磁分离,弃上清液后,加入20 mL 浓度为2 mM 的HAuCl4水溶液中混匀,再逐滴加入新配制的1 mL浓度为200 mM的盐酸羟胺水溶液,搅拌反应 30 min,然后磁分离并弃去上层清液,即可得到金纳米壳磁性PLGA微胶囊(Fe3O4@PLGA@Au);
(8)将Fe3O4@PLGA@Au悬液加入新配制的 8 mL 浓度为 0.01 mg/mL 的mPEG5000-SH水溶液中,搅拌反应 1 h,之后使用磁分离,去离子水洗涤两次,重新悬浮后转入冻干瓶,加液氮预冷,使用冻干机在-90 ℃下真空干燥 3 d,即可得到表面PEG修饰的金纳米壳磁性PLGA微胶囊(Fe3O4@PLGA@Au-PEG)。
实施例2
(1)将100 mL 含10.82 g FeCl3·6H2O(0.04 mol)、3.98 g FeCl2·4H2O(0.02 mol)的水溶液置于三口烧瓶中,通氮气,机械搅拌(3000 rpm)半小时后,缓慢滴加10 mol/L的NaOH溶液50 mL。在常温下搅拌1 h,再升温至90℃,保温2 h。再逐滴加入 10 mL 油酸,继续反应30 min。待反应结束之后将体系冷却至室温,用磁铁吸引将产物分离,加入大量丙酮沉淀,磁分离,再分散在20 mL水中,加热至50℃,使丙酮挥发,并用去离子水和乙醇分别洗涤三次,40℃真空干燥,即得油酸修饰的Fe3O4纳米颗粒;
(2)取1000 mg的聚乳酸羟基乙酸(PLGA)和600 mg 油酸修饰的Fe3O4纳米颗粒分散在20 mL二氯甲烷中,充分溶解,作为有机相溶液A;
(3)将新配制的 0.5 mL 浓度为 4wt%的(NH4)2CO3水溶液作为内水相,加入有机相溶液A中形成乳液B;
(4)将乳液B逐滴地加到20 mL预冷的聚乙烯醇(PVA)外水相溶液中,冰水浴条件下用超声波细胞破碎仪进行乳化,形成复乳液C后,在通风橱中使二氯甲烷尽量自然挥发,然后磁吸附沉淀洗涤后即得包覆Fe3O4的PLGA微米颗粒(Fe3O4@PLGA);
(5)取80 mg Fe3O4@PLGA微米颗粒悬浮在6 mL 浓度为1 mg/mL的聚烯丙基胺盐酸盐(PAH)溶液中,混合均匀,磁吸附沉淀以去除剩余未吸附的PAH,沉淀即为PAH 包覆的Fe3O4@PLGA微米颗粒;
(6)取氯金酸和柠檬酸钠的混合溶液 200 mL,其中氯金酸的浓度为10 mM,柠檬酸钠的浓度为5wt%,加入1 mL含0.375wt%硼氢化钠(NaBH4)的柠檬酸钠溶液后,剧烈搅拌1 min,即得到柠檬酸根稳定的金纳米粒子水溶液;
(7)将(5)制备的颗粒分散于(6)所得溶液中,充分混合吸附30 min后,磁分离,弃上清液后,加入20 mL 浓度为2 mM 的HAuCl4水溶液中混匀,再逐滴加入新配制的1 mL浓度为200 mM的盐酸羟胺水溶液,搅拌反应 30 min,然后磁分离并弃去上层清液,即可得到金纳米壳磁性PLGA微胶囊(Fe3O4@PLGA@Au);
(8)将Fe3O4@PLGA@Au悬液加入新配制的 8 mL 浓度为 0.01 mg/mL 的mPEG4000-SH水溶液中,搅拌反应 1 h,之后使用磁分离,去离子水洗涤两次,重新悬浮后转入冻干瓶,加液氮预冷,使用冻干机在-90℃下真空干燥 3 d,即可得到表面PEG修饰的金纳米壳磁性PLGA微胶囊(Fe3O4@PLGA@Au-PEG)。
实施例3
(1)将100 mL含 10.82 g FeCl3·6H2O(0.04 mol)、3.98 g FeCl2·4H2O(0.02 mol)的水溶液置于三口烧瓶中,通氮气,机械搅拌(3000 rpm)半小时后,缓慢滴加10 mol/L的NaOH溶液50 mL。在常温下搅拌1 h,再升温至90℃,保温2 h。再逐滴加入 10 mL 油酸,继续反应30 min。待反应结束之后将体系冷却至室温,用磁铁吸引将产物分离,加入大量丙酮沉淀,磁分离,再分散在20 mL水中,加热至50℃,使丙酮挥发,并用去离子水和乙醇分别洗涤三次,40℃真空干燥,即得油酸修饰的Fe3O4纳米颗粒;
(2)取800 mg的聚乳酸羟基乙酸(PLGA)和300 mg 油酸修饰的Fe3O4纳米颗粒分散在20mL二氯甲烷中,充分溶解,作为有机相溶液A;
(3)将新配制的 0.5 mL 浓度为 4wt%的(NH4)2CO3水溶液作为内水相,加入有机相溶液A中形成乳液B;
(4)将乳液B逐滴地加到20 mL预冷的聚乙烯醇(PVA)外水相溶液中,冰水浴条件下用超声波细胞破碎仪进行乳化,形成复乳液C后,在通风橱中使二氯甲烷尽量自然挥发,然后磁吸附沉淀洗涤后即得包覆Fe3O4的PLGA微米颗粒(Fe3O4@PLGA);
(5)取100 mg Fe3O4@PLGA微米颗粒悬浮在16 mL 浓度为1 mg/mL的聚烯丙基胺盐酸盐(PAH)溶液中,混合均匀,磁吸附沉淀以去除剩余未吸附的PAH,沉淀即为PAH 包覆的Fe3O4@PLGA微米颗粒;
(6)取取氯金酸和柠檬酸钠的混合溶液 400 mL,其中氯金酸的浓度为10 mM,柠檬酸钠的浓度为5wt%,加入1 mL含0.375wt%硼氢化钠(NaBH4)的柠檬酸钠溶液后,剧烈搅拌1 min,即得到柠檬酸根稳定的金纳米粒子水溶液;
(7)将(5)制备的颗粒分散于(6)所得溶液中,充分混合吸附30 min后,磁分离,弃上清液后,加入20 mL 浓度为2 mM 的HAuCl4水溶液中混匀,再逐滴加入新配制的1 mL浓度为200 mM的盐酸羟胺水溶液,搅拌反应 30 min,然后磁分离并弃去上层清液,即可得到金纳米壳磁性PLGA微胶囊(Fe3O4@PLGA@Au);
(8)将Fe3O4@PLGA@Au悬液加入新配制的 8 mL 浓度为 0.01 mg/mL 的mPEG4000-SH水溶液中,搅拌反应 1 h,之后使用磁分离,去离子水洗涤两次,重新悬浮后转入冻干瓶,加液氮预冷,使用冻干机在-90℃下真空干燥 3 d,即可得到表面PEG修饰的金纳米壳磁性PLGA微胶囊(Fe3O4@PLGA@Au-PEG)。
以上所述仅为本发明的较佳实施方式,凡依本发明申请专利范围所做的均等变化与修饰,皆应属本发明的涵盖范围。
Claims (6)
1.一种金纳米壳磁性液态氟碳纳米微囊的制备方法,其特征在于:采用超声-乳匀法,以聚乳酸-羟基乙酸共聚物为成膜材料,内载氧化铁纳米粒子为造影剂,外包覆金纳米壳层作为光吸收剂,制备得到金纳米壳磁性PLGA微胶囊。
2.根据权利要求1所述的制备方法,其特征在于:包括以下步骤:
(1)将100 mL 含10.82 g FeCl3·6H2O、3.98 g FeCl2·4H2O的水溶液置于三口烧瓶中,通氮气,机械搅拌半小时后,缓慢滴加10 mol/L的NaOH溶液50 mL,在常温下搅拌1 h,再升温至90℃,保温2 h,再逐滴加入 10 mL 油酸,继续反应 30 min,待反应结束之后将体系冷却至室温,用磁铁吸引将产物分离,加入大量丙酮沉淀,磁分离,再分散在20 mL水中,加热至50℃,使丙酮挥发,并用去离子水和乙醇分别洗涤三次,40℃真空干燥,即得油酸修饰的Fe3O4纳米颗粒;
(2)取100-1000 mg的PLGA和30-600 mg 油酸修饰的Fe3O4纳米颗粒分散在3-20 mL二氯甲烷中,充分溶解,作为有机相溶液A;
(3)将新配制的 0.5-10 mL 浓度为 4wt%的(NH4)2CO3水溶液作为内水相,加入有机相溶液A中形成乳液B;
(4)将乳液B逐滴地加到20-200 mL预冷的聚乙烯醇外水相溶液中,冰水浴条件下用超声波细胞破碎仪进行乳化,形成复乳液C后,在通风橱中使二氯甲烷自然挥发,然后磁吸附沉淀洗涤后即得Fe3O4@PLGA微米颗粒;
(5)取80-1000 mg Fe3O4@PLGA微米颗粒悬浮在6-200 mL 浓度为1 mg/mL的聚烯丙基胺盐酸盐溶液中,混合均匀,磁吸附沉淀以去除剩余未吸附的聚烯丙基胺盐酸盐,沉淀即为聚烯丙基胺盐酸盐包覆的Fe3O4@PLGA微米颗粒;
(6)取氯金酸和柠檬酸钠的混合溶液 100-500 mL,其中氯金酸的浓度为10 mM,柠檬酸钠的浓度为5wt%,加入 1-5 mL含0.375wt%硼氢化钠的柠檬酸钠溶液后,剧烈搅拌1 min,即得到柠檬酸根稳定的金纳米粒子水溶液;
(7)将(5)制备的颗粒分散于(6)所得溶液中,充分混合吸附30 min后,磁分离,弃上清液后,加入20-200 mL 浓度为2 mM 的HAuCl4水溶液中混匀,再逐滴加入新配制的1-80 mL浓度为200 mM的盐酸羟胺水溶液,搅拌反应 30 min,然后磁分离并弃去上层清液,即可得到Fe3O4@PLGA@Au;
(8)将Fe3O4@PLGA@Au悬液加入新配制的 8-100 mL 浓度为 0.01 mg/mL 的mPEG4000-SH水溶液中,搅拌反应 1 h,之后使用磁分离,去离子水洗涤两次,重新悬浮后转入冻干瓶,加液氮预冷,使用冻干机在-90℃下真空干燥 3 d,即可得到Fe3O4@PLGA@Au-PEG。
3.根据权利要求2所述的制备方法,其特征在于:步骤(5)利用聚电解质逐层沉积的原理,使用聚阳离子电解质,通过静电吸附的方法将带正电的聚电解质聚烯丙基胺盐酸盐吸附于PLGA表面。
4.根据权利要求2所述的制备方法,其特征在于:步骤(7)在聚电解质聚烯丙基胺盐酸盐的帮助下,在其表面静电吸附金纳米粒子,再利用表面原位引晶技术,形成金纳米壳层。
5.根据权利要求2所述的制备方法,其特征在于:步骤(8)使用冷冻干燥法除去微囊中的水相,使微囊内部形成微小空穴;使用巯基修饰的PEG与表面Au共价结合。
6.根据权利要求1-5任一所述的制备方法,其特征在于:通过双乳化-溶剂挥发法和交替的电位变化,来包覆Fe3O4和吸附金纳米粒,制得金纳米壳磁性PLGA微胶囊。
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CN109769807A (zh) * | 2018-11-14 | 2019-05-21 | 浙江农林大学 | 一种具有双分子结构的缓释灭藻微胶囊及其制备方法 |
CN111701032A (zh) * | 2020-06-23 | 2020-09-25 | 重庆大学附属肿瘤医院 | 兼具药物控释及成像功能的介孔氧化硅复合体的制备方法 |
CN115227838A (zh) * | 2022-05-12 | 2022-10-25 | 昆明医科大学 | 一种适配体结合纳米微泡构建纳米组装体的制备方法及其应用 |
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CN109769807A (zh) * | 2018-11-14 | 2019-05-21 | 浙江农林大学 | 一种具有双分子结构的缓释灭藻微胶囊及其制备方法 |
CN111701032A (zh) * | 2020-06-23 | 2020-09-25 | 重庆大学附属肿瘤医院 | 兼具药物控释及成像功能的介孔氧化硅复合体的制备方法 |
CN115227838A (zh) * | 2022-05-12 | 2022-10-25 | 昆明医科大学 | 一种适配体结合纳米微泡构建纳米组装体的制备方法及其应用 |
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