Peptide-mediated targeting to tumor blood vessels of lung cancer for drug delivery
Peptide-mediated targeting to tumor blood vessels of lung cancer for drug delivery
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DOI：
10.1158/0008-5472.can-07-2233
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发表时间：
2007-11-15
期刊：
影响因子：
11.2
通讯作者：
Wu, Han-Chung
中科院分区：
文献类型：
--
作者：
Lee, Tong-Young;Lin, Chin-Tarng;Wu, Han-Chung
抗血管生成疗法治疗癌症具有高效、低毒的前景。利用体内噬菌体展示技术鉴定肿瘤血管特异性多肽。在携带人类肿瘤的严重联合免疫缺陷小鼠中，SP5-52肽识别肿瘤新生血管，但不识别正常血管。竞争抑制实验表明，人工合成的多肽能够抑制PC5-52噬菌体颗粒与肿瘤的结合。几个选定的噬菌体克隆显示了共同的基序，即脯氨酸-丝氨酸-脯氨酸，该基序对于多肽与肿瘤新生血管的结合至关重要。SP552多肽还与血管内皮生长因子刺激的人脐静脉内皮细胞和人肺癌手术标本的血管结合。此外，在活体噬菌体展示实验后，该靶向噬菌体被证明是来自八种不同类型的人肿瘤移植瘤的肿瘤组织的家园。携带阿霉素的SP5-52肽连接脂质体增强了药物的治疗效果，显著减少了肿瘤血管，并导致了人肺癌和口腔癌移植瘤小鼠更高的存活率。目前的研究表明，与传统的抗癌药物治疗相比，配体靶向治疗提供了更好的治疗效果，并且SP5-52肽特异性地靶向肿瘤新生血管，是向实体肿瘤靶向递送药物的良好候选者。
Antiangiogenesis therapies for the treatment of cancers hold the promise of high efficacy and low toxicity. In vivo phage display was used to identify peptides specifically targeting tumor blood vessels. The peptide SP5-52 recognized tumor neovasculature but not normal blood vessels in severe combined immunodeficiency mice bearing human tumors. Synthetic peptide was shown to inhibit the binding of PC5-52 phage particles to the tumor mass in the competitive inhibition assay. Several selected phage clones displayed the consensus motif, proline-serine-proline, and this motif was crucial for peptide binding to the tumor neovasculature. SP552 peptides also bound vascular endothelial growth factor-stimulated human umbilical vein endothelial cells and blood vessels of human lung cancer surgical specimens. Furthermore, this targeting phage was shown to home to tumor tissues from eight different types of human tumor xenografts following in vivo phage display experiments. An SP5-52 peptide-linked liposome carrying doxorubicin enhanced the therapeutic efficacy of the drug, markedly decreased tumor blood vessels, and resulted in higher survival rates of human lung and oral cancer-bearing xenograft mice. The current study indicates that ligand-targeted therapy offers improved therapeutic effects over conventional anticancer drug therapy, and that the peptide SP5-52 specifically targets tumor neovasculature and is a good candidate for targeted drug delivery to solid tumors.