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）mV。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TF-LP、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 optimize the preparation of liposome particles co-modified with transferrin and arginine-glycine-aspartic acid (RGD) peptide and evaluate the efficiency of the prepared particles in targeting lung cancer cells in vitro and in vivo ． Methods： Liposome particles modified, respectively, with vehicle (LP), transferrin (TF-LP), RGD peptide (RGD-LP) and TF and RGD (TF/RGD-LP) were prepared by a film-ultrasonic method. The appearance, size and Zeta potential of the particles were determined. The efficiency of these various particles in targeting lung cancer cells were assessed by cellular uptake assays in A549 cells and in a multicellular tumor spheroid model in vitro and by a imaging assay in solid tumors in nude mice in vivo . Results： TF/RGD-LP particles were 122.8±11.5 nm in diameter with an average Zeta potential of 6.4±3.85 mV. TF/RGF-LP particles were uptake by A549 cells 2.8, 2.2 and 3.9 times more efficiently than TF-LP, RGD-LP and LP particles respectively. In consistent with in vitro findings, TF/RGD-LP particles were most efficient among the types of particles tested in penetrating solid tumor spheroids in vivo. Conclusion： Co-modification with transferrin and RGD peptide can enhance the ability of liposomes to penetrate lung cancer cells and thus may offer a better antitumor agent delivery system.

河南省卫生厅课题资助项目（No.1203068）