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目的:构建转铁蛋白(transferrin,TF)与整合素受体结合肽(RGD)共修饰脂质体(TF/RGD-LP),从体内外评价TF/RGD-LP的肺癌组织细胞靶向性。方法:薄膜分散法制备整合素受体结合肽RGD修饰的脂质体(RGD-LP),采用后插入法制备TF与RGD共修饰脂质体TF/RGD-LP,分析脂质体的理化性质。将肺癌A549细胞分为TF/RGD-LP、TF-LP、RGD-LP和LP组,每组设5个复孔。细胞摄取实验和肿瘤细胞球穿透实验研究TF/RGD-LP与肺癌A549细胞的亲和力和肿瘤组织的穿透能力,通过荷瘤裸鼠活体成像实验检测TF/RGD-LP的肺癌组织细胞靶向性。结果:所制备TF/RGD-LP粒径为(122.8±11.5)nm,电位为(6.4±3.85)m V。体外细胞摄取实验表明,肺癌A549细胞对TF/RGD-LP的摄取效率分别是TFLP、RGD-LP和LP的2.8、2.2和3.9倍,TF-LP(P=0.006)、RGD-LP(P=0.007)和LP(P=0.001)的主效应有统计学意义,三者间有交互效应(P=0.006);肿瘤细胞球摄取实验以及裸鼠肿瘤组织活体成像实验表明,TF/RGD-LP具有良好的肺癌组织靶向性。结论:TF/RGD-LP具有良好的肺癌组织细胞靶向性,是一种潜在的肺癌组织细胞靶向给药系统。
OBJECTIVE: To construct the liposomes (TF / RGD-LP) co-modified with transferrin (TF) and integrin receptor binding peptide (RGD) and to evaluate the cellular targeting of TF / RGD-LP in vitro and in vivo . METHODS: RGD-LP was prepared by thin-film dispersion method. The liposome TF / RGD-LP was co-modified with TF and RGD by post-insertion method. The physicochemical properties of the liposomes were analyzed . A549 lung cancer cells were divided into TF / RGD-LP, TF-LP, RGD-LP and LP groups, each set of five complex wells. Cell Uptake Test and Tumor Cell Ball Penetration Experiment The affinity of TF / RGD-LP to lung cancer A549 cells and the penetration ability of tumor tissue were studied. The lung cancer tissue cell targets of TF / RGD-LP were detected by in vivo imaging of tumor-bearing nude mice Sex. Results: The particle size of TF / RGD-LP was (122.8 ± 11.5) nm and the potential was (6.4 ± 3.85) mV. In vitro cell uptake experiments showed that the uptake efficiency of TF / RGD-LP in lung cancer A549 cells were 2.8, 2.2 and 3.9 times higher than that of TFLP, RGD-LP and LP respectively (P = 0.006) 0.007) and LP (P = 0.001), the interaction between them was significant (P = 0.006). The experiments of tumor cell uptake and in vivo imaging of tumor tissue in nude mice showed that TF / RGD- Good lung cancer tissue targeting. CONCLUSION: TF / RGD-LP has good cell targeting of lung cancer tissue and is a potential target-directed delivery system for lung cancer cells.