pH敏感性的脂质-介孔硅核/壳纳米粒作为抗肿瘤药物新型载体的初步研究

Preliminary study on pH-sensitive lipid bilayer-coated mesoporous silica nanoparticles as a novel drug carrier for antitumor drug

本文拟构建一种具有pH敏感性的脂质介孔硅核/壳纳米粒(lipid bilayer-coated mesoporous silicananoparticles,LMSNs)以提高抗肿瘤药物对肿瘤细胞的杀伤活性。采用水热薄膜水化分散法合成制备了包载盐酸伊立替康(irinotecan,CPT-11)的脂质介孔硅核/壳纳米粒(lipid coated mesoporous silica nanoparticles loaded with CPT-11,CPT-11-LMSNs),并对其进行了形态、粒度和释放度的表征。同时,以人乳腺癌细胞MCF-7为细胞模型,考察了载体的细胞摄取定位、药物胞内蓄积量和抗肿瘤活性。研究结果表明:LMSNs在透射电镜下呈圆整球形,平均粒径为(120.27±5.91)nm。载体在体外模拟正常生理环境中CPT-11泄露量低,而在模拟肿瘤胞内环境中快速释药,表明该载体的释药行为具有pH响应性。另外,LMSNs可有效提高MCF-7细胞对药物的摄取量,显著增加CPT-11对肿瘤细胞的杀伤力,将CPT-11介孔硅纳米粒(CPT-11-MSNs)的胞内药物累积量提高2.1倍,半数抑制浓度(IC50)降低1.4倍。

This study plans to prepare lipid bilayer-coated mesoporous silica nanoparticles （LMSNs） which are pH sensitive with core-shell structure to improve the tumor cell lethality of antitumor drug. The lipid coated mesoporous silica nanoparticles loaded with irinotecan （CPT-11） （CPT-11-LMSNs） were prepared by hot water- film hydration method, and the characterized its morphology, particle size and release in vitro. Meanwhile, the intracellular uptake and cell toxicity of CPT-11-LMSNs and intracellular accumulation of CPT-11 were evaluated on human breast carcinoma cell line （MCF-7）. The results indicated that the mean diameter of the spherical LMSNs was （120.27 ± 5.91） nm. The slow release in simulated normal physiological conditions and a rapid release under simulated intracellular condition demonstrated the pH sensitivity of CPT-11-MSNs in vitro. Moreover, the CPT-11-LMSN could improve the intracellular CPT-11 cumulant 2.1 times and reduce half maximal inhibitory concentration （IC50） values of CPT-11 1.4 times compared with CPT-11-MSNs, demonstrating a stronger cell lethality.