论文部分内容阅读
本文拟构建一种新型的脂质-磷酸钙核/壳纳米粒(lipid bilayer-coated calcium phosphate nanoparticles,LCAPNs)可在胞内溶解实现迅速释药,以提高抗肿瘤药物对肿瘤细胞的杀伤活性。采用薄膜分散法合成制备了包载紫杉醇(paclitaxel,PTX)的脂质-磷酸钙核/壳纳米粒(lipid bilayer-coated calcium phosphate nanoparticles loaded with PTX,PTX-LCAPNs),并对其进行形态、粒度和体外释放行为的表征。同时,以人肝癌细胞Huh-7为细胞模型,考察载体的细胞摄取、胞内溶解特性、药物胞内蓄积量和抗肿瘤活性。研究结果表明:LCAPNs在透射电镜下呈球形,平均粒径为124.73±6.41 nm。载体在体外模拟正常生理p H条件下PTX泄漏量低,而在胞内酸性p H环境中快速释药。另外,LCAPNs可有效提高Huh-7细胞对药物的摄取量,并且在胞内溶解以快速释药。PTXLCAPNs显著增加PTX对肿瘤细胞的杀伤力,将包载紫杉醇的磷酸钙纳米粒(calcium phosphate nanoparticles loaded with PTX,PTX-CAPNs)的胞内药物浓度提高了1.7倍,半数抑制浓度(IC50)降低了约5倍,抗肿瘤效果显著增强。
In this paper, a new type of lipid bilayer-coated calcium phosphate nanoparticles (LCAPNs) can be prepared to release rapidly in intracellular solution to improve the killing activity of antitumor drugs on tumor cells. The lipid bilayer-coated calcium phosphate nanoparticles loaded with PTX (PTX-LCAPNs) was prepared by thin-film dispersion method and its morphology, particle size And characterization of in vitro release behavior. At the same time, Huh-7 human hepatocellular carcinoma cell model was used to investigate the cellular uptake, intracellular dissolution, intracellular accumulation and anti-tumor activity of the drug. The results showed that LCAPNs were spherical under transmission electron microscope with average particle size of 124.73 ± 6.41 nm. The vector showed low PTX leakage in vitro under simulated physiological pH conditions and rapidly released in an intracellular acidic pH environment. In addition, LCAPNs can effectively increase the uptake of drugs by Huh-7 cells and dissolve intracellularly for rapid release. PTXLCAPNs significantly increased the lethality of PTX on tumor cells, increased the intracellular drug concentration of paclitaxel-loaded calcium phosphate nanoparticles (PTX-CAPNs) by 1.7-fold, and decreased the half-maximal inhibitory concentration (IC50) About 5 times, anti-tumor effect was significantly enhanced.