Department of Pathobiology, Auburn University, Auburn, Alabama 36849, USA.
Nanomedicine. 2010 Aug;6(4):538-46. doi: 10.1016/j.nano.2010.01.005. Epub 2010 Feb 4.
Tumor-specific cytotoxicity of drugs can be enhanced by targeting them to tumor receptors using tumor-specific ligands. Phage display offers a high-throughput approach to screen for the targeting ligands. We have successfully isolated phage fusion peptides selective and specific for PC3 prostate cancer cells. Also, we have demonstrated a novel approach of targeting liposomes through tumor-specific phage fusion coat proteins, exploiting the intrinsic properties of the phage coat protein as an integral membrane protein. Here we describe the production of Rhodamine-labeled liposomes as well as doxorubicin-loaded long-circulating liposomes targeted to PC3 prostate tumor cells via PC-specific phage peptides, as an extension of our previous studies. Targeting of labeled liposomes was demonstrated using fluorescence microscopy as well as flow cytometry. Targeting of doxorubicin-loaded liposomes enhanced their cytotoxic effect against PC3 cells in vitro, indicating a possible therapeutic advantage. The simplicity of the approach for generating targeted liposomes coupled with the ability to rapidly obtain tumor-specific phage fusion proteins via phage display may contribute to a combinatorial system for the production of targeted liposomal therapeutics for advanced stages of prostate tumor. From the clinical editor: This paper demonstrates targeting cytotoxic agents to tumor receptors using tumor-specific ligands. The authors describe the production of Rhodamine-labeled liposomes as well as doxorubicin loaded long circulating liposomes targeted to PC3 prostate tumor cells via PC-specific phage peptides. This approach may be especially relevant for advanced prostate tumors.
药物的肿瘤特异性细胞毒性可以通过使用肿瘤特异性配体将其靶向肿瘤受体来增强。噬菌体展示提供了一种高通量筛选靶向配体的方法。我们已经成功地分离出了对 PC3 前列腺癌细胞具有选择性和特异性的噬菌体融合肽。此外，我们还展示了一种通过肿瘤特异性噬菌体融合外壳蛋白靶向脂质体的新方法，利用噬菌体外壳蛋白作为整合膜蛋白的固有特性。在这里，我们描述了通过 PC 特异性噬菌体肽靶向 PC3 前列腺肿瘤细胞的 Rhodamine 标记脂质体以及阿霉素负载的长循环脂质体的生产，这是我们之前研究的扩展。使用荧光显微镜和流式细胞术证明了标记脂质体的靶向性。载药脂质体的靶向性增强了它们对 PC3 细胞的体外细胞毒性作用，表明可能具有治疗优势。生成靶向脂质体的方法简单，并且能够通过噬菌体展示快速获得肿瘤特异性噬菌体融合蛋白，这可能有助于开发针对前列腺肿瘤晚期的靶向脂质体治疗的组合系统。临床编辑评论：本文证明了使用肿瘤特异性配体将细胞毒性剂靶向肿瘤受体。作者描述了通过 PC 特异性噬菌体肽靶向 PC3 前列腺肿瘤细胞的 Rhodamine 标记脂质体以及阿霉素负载的长循环脂质体的生产。这种方法可能对晚期前列腺肿瘤尤其相关。
