The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjian, People's Republic of China.
Int J Nanomedicine. 2010 Dec 22;6:59-69. doi: 10.2147/IJN.S14601.
Phage display technology has been demonstrated to be a powerful tool for screening useful ligands that are capable of specifically binding to biomarkers on the surface of tumor cells. The ligands found by this technique, such as peptides, have been successfully applied in the fields of early cancer diagnostics and chemotherapy. In this study, a novel nonsmall cell lung cancer-targeting peptide (LCTP, sequence RCPLSHSLICY) was screened in vivo using a Ph.D.-C7C(™) phage display library. In order to develop a universal tumor-targeting drug carrier, the LCTP and fluorescence-labeled molecule (FITC) were conjugated to an acetylated polyamidoamine (PAMAM) dendrimer of generation 4 (G4) to form a PAMAM-Ac-FITC-LCTP conjugate. The performance of the conjugate was first tested in vitro. In vitro results of cell experiments analyzed by flow cytometry and inverted fluorescence microscopy indicated that PAMAM-Ac-FITC-LCTP was enriched more in NCI-H460 cells than in 293T cells, and cellular uptake was both time- and dose-dependent. The tissue distribution of the conjugate in athymic mice with lung cancer xenografts was also investigated to test the targeting efficiency of PAMAM-Ac-FITC-LCTP in vivo. The results showed that LCTP can effectively facilitate the targeting of PAMAM-Ac-FITC-LCTP to nonsmall cell lung cancer cells and tumors. These results suggest that the LCTP-conjugated PAMAM dendrimer might be a promising drug carrier for targeted cancer diagnosis and treatment.
噬菌体展示技术已被证明是筛选能够特异性结合肿瘤细胞表面生物标志物的有用配体的强大工具。该技术发现的配体，如肽，已成功应用于癌症早期诊断和化疗领域。在这项研究中，使用 Ph.D.-C7C(™)噬菌体展示文库在体内筛选了一种新型非小细胞肺癌靶向肽（LCTP，序列为 RCPLSHSLICY）。为了开发通用的肿瘤靶向药物载体，将 LCTP 和荧光标记分子（FITC）与乙酰化聚酰胺胺（PAMAM）树枝状大分子的第 4 代（G4）缀合，形成 PAMAM-Ac-FITC-LCTP 缀合物。首先在体外测试了该缀合物的性能。通过流式细胞术和倒置荧光显微镜分析的细胞实验的体外结果表明，PAMAM-Ac-FITC-LCTP 在 NCI-H460 细胞中的富集程度高于 293T 细胞，并且细胞摄取具有时间和剂量依赖性。还研究了该缀合物在带有肺癌异种移植的无胸腺小鼠中的组织分布，以测试 PAMAM-Ac-FITC-LCTP 在体内的靶向效率。结果表明，LCTP 可以有效地促进 PAMAM-Ac-FITC-LCTP 对非小细胞肺癌细胞和肿瘤的靶向。这些结果表明，LCTP 缀合的 PAMAM 树枝状大分子可能是一种有前途的用于靶向癌症诊断和治疗的药物载体。
