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Anti‐neovascular therapy by liposomal drug targeted to membrane type‐1 matrix metalloproteinase
Author(s) -
Kondo Masami,
Asai Tomohiro,
Katanasaka Yasufumi,
Sadzuka Yasuyuki,
Tsukada Hideo,
Ogino Koichi,
Taki Takao,
Baba Kazuhiko,
Oku Naoto
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11526
Subject(s) - liposome , matrix metalloproteinase , peptide , cancer research , drug delivery , angiogenesis , umbilical vein , mmp1 , chemistry , medicine , biochemistry , in vitro , organic chemistry , gene expression , gene
Because membrane type‐1 matrix metalloproteinase (MT1‐MMP) is expressed specifically on the angiogenic endothelium as well as tumor cells, an agent possessing the ability to bind to this molecule might be useful as a tool for active targeting of tumor angiogenic vessels. Based on the sequences of peptide substrates of MT1‐MMP, which had been determined by using a phage‐displayed peptide library, we examined the binding ability of peptide‐modified liposomes for endothelial cells and targeting ability for tumor tissues by positron emission tomography (PET). Liposomes modified with stearoyl‐Gly‐Pro‐Leu‐Pro‐Leu‐Arg (GPLPLR‐Lip) showed high binding ability to human umbilical vein endothelial cells and accumulated in the tumor about 4‐fold more than did the unmodified liposomes. Because we reported previously 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, strongly suppressed tumor growth when delivered in liposomes modified with another angiogenic homing peptide, we examined the antitumor activity of DPP‐CNDAC entrapped in GPLPLR‐Lip. DPP‐CNDAC/GPLPLR‐Lip showed significant tumor growth suppression compared to DPP‐CNDAC/unmodified liposomes. These results suggest that DPP‐CNDAC‐liposomes modified with MT1‐MMP‐targeted peptide are useful for cancer anti‐neovascular therapy (ANET), namely, tumor growth suppression by damage to angiogenic endothelial cells. © 2003 Wiley‐Liss, Inc.