Targeted delivery of anticancer drugs to tumor vessels by use of liposomes modified with a peptide identified by phage biopanning with human endothelial progenitor cells

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Abstract

As tumor angiogenic vessels are critical for tumor growth and express different molecules on their surface from those on normal vessels, these vessels are expected to be an ideal target for anticancer drug delivery systems. It was previously reported that endothelial progenitor cells (EPCs) are involved in angiogenesis, tumor growth, and metastasis, and that EPCs show gene expression patterns similar to those of tumor endothelial cells. In the present study, a tumor vessel-targeting peptide, ASSHN, was identified from a phage-display peptide library by in vitro biopanning with human EPCs (hEPCs) and in vivo biopanning using angiogenesis model mice prepared by the dorsal air sac method. Phage clones displaying ASSHN peptide showed a marked affinity for hEPCs in vitro, and also for tumor vessels in vivo. PEGylated liposomes modified with the ASSHN peptide (ASSHN-Lip) were designed and prepared for the delivery of anticancer agents. Confocal images showed that ASSHN-Lip clearly bound to hEPCs in vitro and tumor vessels, and also showed extravasation from the vessels. The administration of doxorubicin-encapsulated ASSHN-Lip into Colon26 NL-17-bearing mice significantly suppressed tumor growth compared with doxorubicin-encapsulated PEGylated liposomes. These results suggest that the delivery of anticancer agents with ASSHN-Lip could be useful for targeted cancer therapy.

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