title: Radiation-induced galectin-1 by endothelial cells: a promising molecular target for preferential drug delivery to the tumor vasculature.
abstract: The present study reports on a new strategy for selective, radiation therapy-amplified drug delivery using an antiangiogenic 33-a.a., tumor vasculature-targeting ligand, anginex, to improve the therapeutic ratio for strategies developed against solid tumors. Our findings indicate that galectin-1 is (a) one of the major receptors for anginex (b) overexpressed by tumor neovasculature and (c) further specifically upregulated in endothelial cells in response to radiation exposure as low as 0.5 Gy. An investigation of [18]-F-labeled anginex biodistribution in SCK tumors indicates that anginex is an effective targeting molecule for image and radiation-guided therapy of solid tumors. An anginex-conjugated liposome capable of being loaded with drug was shown to selectively target endothelial cells post-radiation. The presence of endothelial cells in a three-dimensional co-culture system with tumor cells developed to study tumor/endothelial cell interactions in vitro led to higher levels of galectin-1 and showed a further increase in expression upon radiation exposure when compared to tumor cell spheroids alone. Similar increase in galectin-1 was observed in tumor tissue originating from the tumor-endothelial cell spheroids in vivo and radiation exposure further induced galectin-1 in these tumors. The overall results suggest feasibility of using a clinical or subclinical radiation dose to increase expression of the galectin-1 receptor on the tumor microvasculature to promote delivery of therapeutics via the anginex peptide. This approach may reduce systemic toxicity, overcome drug resistance, and improve the therapeutic efficacy of conventional chemo/radiation strategies.
authors.affiliation: College of Pharmacy, University of Kentucky, 789 S. Limestone Street, Lexington, KY 40536-0596, USA. m.upreti@uky.edu
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Upreti
authors.forename: Azemat
authors.initials: A
authors.lastname: Jamshidi-Parsian
authors.forename: Scott
authors.initials: S
authors.lastname: Apana
authors.forename: Marc
authors.initials: M
authors.lastname: Berridge
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Fologea
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Koonce
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Henry
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Griffin
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000528:radiation effects*; D005260:Female; D037483:Galectin 1 / Q000378:metabolism*; D006801:Humans; D008081:Liposomes; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000175:diagnosis / Q000378:metabolism / Q000532:radiotherapy; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism; D049268:Positron-Emission Tomography; D011485:Protein Binding; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D037483:Galectin 1; D008081:Liposomes; D010455:Peptides; C558923:anginex peptide