Lopez-Barcons Lluis A, Polo Dolores, Llorens Ana, Reig Francesca, Fabra Angels
Departament de Càncer and Metastasis, Institut de Recerca Oncològica (IRO), Gran Via Km 2.7, L'Hospitalet de Llobregat, Barcelona, Catalonia 08907, Spain.
Oncol Rep. 2005 Nov;14(5):1337-43.
In the protein-targeted therapy for cancer, transferrin (Tf) is used to reach a selective and specific target in cancer cells. Tf is used conjugated to chemotherapeutic drugs, insulin, toxins, antibodies, polymers, nanoparticles, lipoplexes and liposomes. Using this latter approach, hydrophobically derivatized Tf was incorporated to liposomal bilayers. The biological activity of Tf-liposome was tested using MXT-B2 cells, a metastatic mammary carcinoma cell line. In Tf binding assays, the Scatchard analysis indicated 4.5x10(5) Tf receptors/cell. In cell growth assays, Tf-liposomes stimulated cell growth in a dose-dependent manner, up to a maximum of 32% of the total free Tf stimulation. Following this, we prepared Tf-liposomes encapsulating adriamycin (ADR) at two different ADR-to-lipid ratios. In vitro cytotoxicity assays against MXT-B2 cells gave IC(50) values 2.1-times lower for Tf-liposomal ADR in comparison to control liposomal ADR. However, similar IC(50) values were found for low ADR-to-lipid ratio Tf-liposomal ADR, as well as for control liposomal ADR. The free Tf added in excess increased the IC(50) value of Tf-liposomal ADR by 51%, while the IC(50) value of control liposomal ADR was unaffected, supporting a receptor-mediated mechanism of targeting by Tf. In addition, the lower IC(50) value is correlated with a higher total of ADR accumulation in the cells.
在癌症的蛋白质靶向治疗中，转铁蛋白（Tf）用于靶向癌细胞中的选择性和特异性靶点。Tf与化疗药物、胰岛素、毒素、抗体、聚合物、纳米颗粒、脂质复合物和脂质体偶联使用。采用后一种方法，将疏水衍生化的Tf掺入脂质体双层中。使用转移性乳腺癌细胞系MXT-B2细胞测试了Tf-脂质体的生物活性。在Tf结合试验中，Scatchard分析表明每个细胞有4.5×10⁵个Tf受体。在细胞生长试验中，Tf-脂质体以剂量依赖性方式刺激细胞生长，最高可达总游离Tf刺激的32%。在此之后，我们制备了两种不同阿霉素（ADR）与脂质比例的包裹ADR的Tf-脂质体。针对MXT-B2细胞的体外细胞毒性试验表明，与对照脂质体ADR相比，Tf-脂质体ADR的IC₅₀值低2.1倍。然而，低ADR与脂质比例的Tf-脂质体ADR以及对照脂质体ADR的IC₅₀值相似。过量添加的游离Tf使Tf-脂质体ADR的IC₅₀值增加了51%，而对照脂质体ADR的IC₅₀值未受影响，这支持了Tf的受体介导靶向机制。此外，较低的IC₅₀值与细胞中ADR的总积累量较高相关。
