Anti‐neovascular therapy by liposomal DPP‐CNDAC targeted to angiogenic vessels
Open Access
- 17 May 2002
- journal article
- Published by Wiley in FEBS Letters
- Vol. 520 (1-3) , 167-170
- https://doi.org/10.1016/s0014-5793(02)02821-1
Abstract
We previously reported that liposomalized 5′‐O‐dipalmitoylphosphatidyl 2′‐C‐cyano‐2′‐deoxy‐1‐β‐D‐arabino‐pentofuranosylcytosine (DPP‐CNDAC), a hydrophobized derivative of the novel antitumor nucleoside CNDAC, is quite useful for cancer therapy. On the other hand, for anti‐neovascular therapy, we recently isolated peptides homing to angiogenic vessels from a phage‐displayed random peptide library, and observed that peptide‐modified liposomal adriamycin strongly suppressed tumor growth, perhaps through damaging angiogenic endothelial cells. In the present study, we modified DPP‐CNDAC‐liposomes with one of the angiogenic homing peptides, APRPG, and examined their antitumor activity. Three doses of APRPG‐modified DPP‐CNDAC‐liposomes (15 mg/kg as CNDAC) strongly inhibited tumor growth compared with the same number of doses of unmodified DPP‐CNDAC‐liposomes. The life span was increased 31.8%, with one completely cured mouse out of the six mice treated. Since the accumulation of liposomes in the tumor tissue was not so much different between APRPG‐liposomes and non‐modified liposomes, the enhanced therapeutic efficacy may be explained as the alteration of targets, i.e. APRPG‐modified DPP‐CNDAC‐liposomes caused tumor growth suppression through damage of angiogenic endothelial cells. Anti‐neovascular therapy promises no drug resistance, and should be effective against essentially any kind of solid tumor; and thus the present results demonstrate another benefit of the therapy, namely, high efficacy of cancer treatment.Keywords
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