Antiangiogenic targeting liposomes increase therapeutic efficacy for solid tumors.
It is known that solid tumors recruit new blood vessels to support tumor growth, but the molecular diversity of receptors in tumor angiogenic vessels might also be used clinically to develop better targeted therapy. In vivo phage display was used to identify peptides that specifically target tumor blood vessels. Several novel peptides were identified as being able to recognize tumor vasculature but not normal blood vessels in severe combined immunodeficiency (SCID) mice bearing human tumors. These tumor-homing peptides also bound to blood vessels in surgical specimens of various human cancers. The peptide-linked liposomes containing fluorescent substance were capable of translocating across the plasma membrane through endocytosis. With the conjugation of peptides and liposomal doxorubicin, the targeted drug delivery systems enhanced the therapeutic efficacy of the chemotherapeutic agent against human cancer xenografts by decreasing tumor angiogenesis and increasing cancer cell apoptosis. Furthermore, the peptide-mediated targeting liposomes improved the pharmacokinetics and pharmacodynamics of the drug they delivered compared with nontargeting liposomes or free drugs. Our results indicate that the tumor-homing peptides can be used specifically target tumor vasculature and have the potential to improve the systemic treatment of patients with solid tumors.
Chang
De-Kuan
DK
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
Chiu
Chien-Yu
CY
Kuo
Szu-Yao
SY
Lin
Wei-Chuan
WC
Lo
Albert
A
Wang
Yi-Ping
YP
Li
Pi-Chun
PC
Wu
Han-Chung
HC
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008081:Liposomes; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019151:Peptide Library; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D008081:Liposomes; D019151:Peptide Library; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D004317:Doxorubicin