Liposomal targeting of the antivascular drug combretastatin to irradiated tumors

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" Liposomal targeting of the antivascular drug combretastatin to irradiated tumors "
Christopher Bruce Pattillo M. F. Kiani

Document Type	:	Latin Dissertation
Language of Document	:	English
Record Number	:	53734
Doc. No	:	TL23688
Call number	:	‭3268190‬
Main Entry	:	Christopher Bruce Pattillo
Title & Author	:	Liposomal targeting of the antivascular drug combretastatin to irradiated tumors\ Christopher Bruce Pattillo
College	:	Temple University
Date	:	2007
Degree	:	Ph.D.
student score	:	2007
Page No	:	134
Abstract	:	We hypothesize that localized irradiation of solid tumors results in inflamed vasculature leading to an over-expression of various adhesion molecules. These adhesion molecules can then be targeted to selectively deliver antivascular drugs to irradiated tumors and delay tumor growth. Our purpose was to successfully target Combretastatin to irradiated tumor vasculature using liposomes as a delivery vehicle and vascular adhesion molecules as targeting ligands. For the first part of this study the antivascular drug Combretastatin was incorporated into liposomes whose surfaces had been modified by the addition of cyclo(Arg-Gly-Asp-D-Phe-Cys) (RGD). The RGD bound on the surface of the liposomeis specifically recognized by the αvβ3 integrin on the luminal surface of tumor vasculature. These RGD coated liposomes were successfully targeted to irradiated B16-F10 melanomas in C57BL male mice resulting in significant tumor growth delay compared to control groups. During the second phase of this study Combretastatin was incorporated into liposomes whose surfaces were modified by the addition of anti-E-selectin (ILs). This antibody is specific for the protein E-selectin which we believe is expressed at a high level post irradiation in mammary tumors. These ILs were successfully targeted to irradiated MCa-4 mammary carcinomas in C3H female mice resulting in significant tumor growth delay compared to control groups. However, ILs were not successfully targeted to an irradiated MCa-35 (more vasculature and less hypoxia then the MCa-4) carcinoma. These findings indicate that ILs (anti-E-selectin and RGD) can be successfully targeted to irradiated murine melanomas (B16-F10) and mammary carcinomas (MCa-4) resulting in significant growth delays.
Subject	:	Applied sciences; Antivascular; Combretastatin; Irradiated tumors; Liposomal targeting; Biomedical research; 0541:Biomedical research
Added Entry	:	M. F. Kiani
Added Entry	:	Temple University