Pasqualini R
La Jolla Cancer Research Center, Burnham Institute, CA 92037, USA.
Q J Nucl Med. 1999 Jun;43(2):159-62.
We have developed an in vivo selection system in which phage capable of selective homing to different tissues are recovered from a phage display peptide library following intravenous administration. Using this strategy, we have isolated several organ and tumor-homing peptides. We have shown that each of those peptides binds to different receptors that are selectively expressed on the vasculature of the target tissue. The tumor-homing peptides bind to receptors that are upregulated in tumor angiogenic vasculature. Targeted delivery of doxorubicin to angiogenic vasculature using these peptides in animal models decreased toxicity and increased the therapeutic efficacy of the drug. Vascular targeting may facilitate the development of other treatment strategies that rely on inhibition of angiogenesis and lead to advances in cancer treatment. Our technology is also likely to extend the potential for targeting of drugs, genes, and radionuclides in the context of many diseases.
我们开发了一种体内筛选系统，在静脉注射后，能够从噬菌体展示肽库中回收能够选择性归巢到不同组织的噬菌体。利用这一策略，我们分离出了几种器官和肿瘤归巢肽。我们已经表明，这些肽中的每一种都与在靶组织脉管系统上选择性表达的不同受体结合。肿瘤归巢肽与肿瘤血管生成脉管系统中上调的受体结合。在动物模型中使用这些肽将阿霉素靶向递送至血管生成脉管系统可降低毒性并提高药物的治疗效果。血管靶向可能有助于开发其他依赖于抑制血管生成的治疗策略，并推动癌症治疗取得进展。我们的技术也可能会扩大在许多疾病背景下靶向药物、基因和放射性核素的潜力。
