具核磁共振成像功能的可再生介孔硅作为抗肿瘤药物新型载体的性能研究

Study on renewable mesoporous silica nanoparticles with magnetic resonance imaging as a novel nano-carrier for antitumor drug

目的构建一种具核磁共振成像(magnetic resonance imaging,MRI)功能的再生含钆介孔硅纳米粒(gadolinium-containing renewable mesoporous silica nanoparticles,rMSN-Gd),探究其作为抗肿瘤药物载体的可行性。方法以稻壳为硅源,通过软模板法制备rMSN-Gd纳米粒。对新型纳米粒形态、粒度、介孔状态、元素含量、生物相容性、载药量、体外释放度等方面进行表征,并检测其在体外与荷瘤BALB/c裸鼠体内MRI成像特点。以抗肿瘤药物盐酸阿霉素为模型药物,以人肝癌HepG2细胞与人肺癌A549细胞为模型,对纳米载体的细胞摄取、体外抗肿瘤活性进行评价。结果rMSN-Gd纳米粒呈球形,分散性良好,平均粒径为150 nm,钆含量为4.7%wt,材料具有良好生物相容性。rMSN-Gd体外与体内均有较好MRI成像能力。载药后,其释药速率呈pH依赖性。纳米粒的细胞摄取效率较高,其对HepG2与A549细胞毒性显著高于游离阿霉素。结论多功能纳米材料rMSN-Gd可以成功作为药物递送系统并整合MRI成像功能实现诊断治疗一体化。

Objective A gadolinium-containing renewable mesoporous silica nanoparticles(rMSN-Gd)with magnetic resonance imaging(MRI)were prepared,and its feasibility for antitumor drugs delivery carrier was explored.Methods The rice husk is used as a silicon source and soft template method was used to prepare rMSN-Gd.The multifunctional nanoparticles were characterized by their morphology,particle size mesoporous state,elemental content,biocompatibility.Drug loading and release were characterized in vitro.The MRI system was used to observe the imaging characteristics in vitro and in vivo.Meanwhile,the intracellular uptake and in vitro antitumor activity of DOX-rMSN-Gd was evaluated on human hepatic carcinoma HepG2 cell line and human lung cancer A549 cell line.Results The prepared rMSN-Gd was spherical and well dispersed.The globular-shaped rMSN-Gd with gadolinium content percentage of 4.7%was approximately 150 nm in diameter.These nanoparticles obtained excellent dispersibility and a regular mesoporous structure.The material has good biocompatibility;in vitro MRI imaging showed concentration gradient;about 30 min after intravenous injection of the material into nude mice,the signal intensity of Hela nude mice was significantly increased.After drug loading,the pH-depend drug release was observed for rMSNs-Gd.In addition,the nanoparticles had higher cell uptake efficiency,and their toxicities to HepG2 and A549 cells were significantly higher than those of free doxorubicin.Conclusion The multifunctional nanomaterial rMSN-Gd can be successfully used as a drug delivery system and combine with MRI functions to achieve diagnostic and therapeutic integration.