mPEG修饰的新藤黄酸介孔硅纳米粒的制备及体外评价

目的：制备甲氧基聚乙二醇（mPEG）修饰的介孔二氧化硅（MSNs）载新藤黄酸（gambogenic acid，GNA）纳米粒（mPEG-GNA-MSNs），以实现对药物的缓释并增强其抗肿瘤活性。方法：采用改良的Stöber法合成氨基改性的MCM-41型介孔二氧化硅（NH₂-MSNs），挥干溶剂法载入GNA，以甲氧基聚乙二醇琥珀酰亚胺基活化酯（mPEG-NHS）与NH₂-MSNs形成酰胺键来制备mPEG以封堵载GNA介孔的二氧化硅纳米粒（mPEG-GNA-MSNs）。通过透射电镜、傅里叶红外光谱、氮气吸-脱附、X射线小角粉末衍射、热重分析等方法对纳米粒进行表征，透析袋法考察mPEG-GNA-MSNs的体外释放规律。采用MTT法考察空白载体和载药纳米粒对人源肝癌细胞（HepG2）和肝正常细胞（LO2）的毒性。结果：制备的mPEG-GNA-MSNs在透射电镜下呈球形，粒径均一；mPEG-GNA-MSNs的载药量和包封率分别为（3.59±0.26）%和（14.52±0.18）%；体外释放结果显示，纳米粒具有明显的缓释作用，48 h释放达到平衡；细胞毒性实验结果表明，mPEG的修饰能够降低载体对HepG2和LO2细胞的毒性，并增强纳米粒对肝癌细胞的毒性。结论：mPEG修饰的介孔二氧化硅纳米粒具有良好的生物安全性，对GNA具有显著的缓释作用，并能增强药物的抗肿瘤活性。

Preparation and in vitro evaluation of gambogenic acid loading mesoporous silica nanoparticles modified with mPEG

OBJECTIVE To prepare mesoporous silica nanoparticles (MSNs) loading gambogenic acid (GNA) nanoparticles modified by methoxy polyethylene glycol (mPEG), to achieve the sustained release of drugs and enhance its antitumor activity.METHODS Amino modified MCM-41 mesoporous silica nanoparticles (NH₂-MSNs) were prepared by modified Stöber's method, GNA was loaded into them by solvent evaporation method, mesoporous silica nanoparticles loaded with GNA and blocked by mPEG (mPEG-GNA-MSNs) were prepared by forming amide bonds between methoxy polyethylene glycol succinimidyl ester (mPEG-NHS) and NH₂-MSNs. The nanoparticles were characterized by transmission electron microscopy, Fourier infrared spectroscopy, nitrogen absorption-desorption, X ray small angle powder diffraction and thermogravimetric analysis. Dialysis bag method was used to investigate the in vitro drug release characteristics. MTT method was used to investigate the cytotoxicity of blank carrier and drug loaded nanoparticles on HepG2 and LO2 cells.RESULTS The prepared mPEG-GNA-MSNs were spherical and uniform in transmission electron microscope. The drug loading and entrapment efficiency of GNA in mPEG-GNA-MSNs were (3.59±0.26)% and (14.52±0.18)%. The in vitro release trial revealed that nanoparticles exhibited a sustained release effect and release of 48 h reached equilibrium. The cytotoxicity test showed that mPEG modification could reduce the toxicity of carrier to HepG2 and LO2 cells, and enhance the cytotoxicity of nanoparticles to hepatoma cells.CONCLUSION Mesoporous silica nanoparticles modified by mPEG have good biological safety, have a significant sustained release effect on GNA, and can enhance the anti-tumor activity of the drug.