VCAM-directed Immunoliposomes Loaded with Vascular– Disrupting Agents for Selective Targeting and Occlusion of the Tumor VasculatureAs a Novel Therapeutic Strategy
As a Novel Therapeutic Strategy
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dc.contributor.advisor | Bendas, Gerd | |
dc.contributor.author | Gosk, Sara | |
dc.date.accessioned | 2020-04-12T14:59:32Z | |
dc.date.available | 2020-04-12T14:59:32Z | |
dc.date.issued | 2008 | |
dc.identifier.uri | https://hdl.handle.net/20.500.11811/3623 | |
dc.description.abstract | Targeting the tumor vasculature and selectively modifying endothelial functions with agents that exert their action on the tumor endothelial cells instead of the tumor cells themselves, is an attractive anti-tumor strategy. Polyethylenglycol modified immunoliposomes (IL) directed against vascular cell adhesion molecule 1 (VCAM), a surface receptor over-expressed on tumor vessels, were prepared and investigated the liposomal targetability in vitro and in vivo. The vascular destructing agents, tumor necrosis factor alpha (TNF-α) and the TNF-α inducing drug, DMXAA, are known to selectively target the tumor endothelium and induce a pro-coagulative state, which leads to a collapse of the tumor vasculature. The hypothesis that TNF-α and DMXAA modulate the coagulative state of the endothelium through the up-regulation of tissue factor (TF) was investigated in vitro. VCAM-targeted and non-targeted liposomes loaded with either TNF-α or DMXAA were formulated and upon administration tumor growth delay was investigated in vivo. In vitro, VCAM antibodies conjugated to PEGylated liposomes through the cyanur anchor displayed specific binding to activated endothelial cells under static conditions, as well as under simulated blood flow conditions. The in vivo targeting of IL was analyzed in mice bearing human Colo 677 tumor xenografts 30 min and 24 h post i.v. injection. Whereas biodistribution studies using [3H]-labeled liposomes displayed only marginal higher tumor accumulation of VCAM targeted vs. unspecific ILs; fluorescence microscopy evaluation revealed that their localization within tumors differed strongly. VCAM targeted ILs accumulated in tumor vessels with increasing intensities from 30 min to 24 h, while control ILs accumulated in the tumor tissue by passive diffusion. | |
dc.language.iso | eng | |
dc.rights | In Copyright | |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | |
dc.subject.ddc | 500 Naturwissenschaften | |
dc.subject.ddc | 570 Biowissenschaften, Biologie | |
dc.subject.ddc | 610 Medizin, Gesundheit | |
dc.title | VCAM-directed Immunoliposomes Loaded with Vascular– Disrupting Agents for Selective Targeting and Occlusion of the Tumor Vasculature | |
dc.title.alternative | As a Novel Therapeutic Strategy | |
dc.type | Dissertation oder Habilitation | |
dc.publisher.name | Universitäts- und Landesbibliothek Bonn | |
dc.publisher.location | Bonn | |
dc.rights.accessRights | openAccess | |
dc.identifier.urn | https://nbn-resolving.org/urn:nbn:de:hbz:5N-14475 | |
ulbbn.pubtype | Erstveröffentlichung | |
ulbbnediss.affiliation.name | Rheinische Friedrich-Wilhelms-Universität Bonn | |
ulbbnediss.affiliation.location | Bonn | |
ulbbnediss.thesis.level | Dissertation | |
ulbbnediss.dissID | 1447 | |
ulbbnediss.date.accepted | 03.06.2008 | |
ulbbnediss.institute | Mathematisch-Naturwissenschaftliche Fakultät : Fachgruppe Pharmazie / Pharmazeutisches Institut | |
ulbbnediss.fakultaet | Mathematisch-Naturwissenschaftliche Fakultät | |
dc.contributor.coReferee | Jaehde, Ulrich |
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