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dc.contributor.authorGill, Jason H.*
dc.contributor.authorBibby, Michael C.*
dc.contributor.authorJensen, S.S.*
dc.contributor.authorShnyder, Steven D.*
dc.date.accessioned2009-12-16T08:30:54Z
dc.date.available2009-12-16T08:30:54Z
dc.date.issued2004
dc.identifier.citationGill, J.H., Bibby, M.C., Jensen, S.S. and Shnyder, S.D. (2004). Secretory phospholipase A2 as a tumor specific trigger for targeted delivery of a novel class of liposomal prodrug anticancer etherlipids. Molecular Cancer Therapeutics. Vol. , No. , pp. .en
dc.identifier.urihttp://hdl.handle.net/10454/4108
dc.descriptionNoen
dc.description.abstractThe use of many common clinically relevant chemotherapeutics is often limited due to insufficient delivery to the tumor and dose-limiting systemic toxicities. Therefore, therapeutics that specifically target tumor cells and are nontoxic to normal cells are required. Here, we report the development of a novel class of liposomes composed of lipid prodrugs, which use the increased secretory phospholipase A2 type IIA (sPLA2) activity of the tumor microenvironment as a trigger for the release of anticancer etherlipids (AEL). Treatment of sPLA2-secreting tumor cells in vitro with liposomes consisting of proAELs resulted in growth inhibition comparable with addition of the AELs alone. Using a specific sPLA2 inhibitor, we showed the low cytotoxicity of the nonhydrolyzed proAEL liposomes and have proven the sPLA2 dependency of the activation of proAELs to cytotoxic AELs. In addition, we showed that our proAEL liposomes circumvent the inherent hemolytic toxicities associated with the use of etherlipids, thereby allowing i.v. administration of such therapeutics as nontoxic prodrug liposomes. Furthermore, using a sPLA2-secreting human colon cancer xenograft model, we showed that the proAEL liposomes are capable of inducing a tumor growth delay in vivo. Taken together, these data support the validity of this novel tumor-selective liposomal prodrug delivery strategy. This new approach also provides a promising system for tumor-selective delivery and release of conventional chemotherapeutics encapsulated in the sPLA2-degradable prodrug liposomes.en
dc.language.isoenen
dc.subjectPhospholipase A2en
dc.subjectTumoursen
dc.subjectTriggeren
dc.subjectProdrugen
dc.subjectEtherlipidsen
dc.subjectChemotherapeuticsen
dc.subjectDrug Deliveryen
dc.subjectCancer Therapeuticsen
dc.titleSecretory phospholipase A2 as a tumor specific trigger for targeted delivery of a novel class of liposomal prodrug anticancer etherlipidsen
dc.status.refereedYesen
dc.typeArticleen
dc.type.versionNo full-text available in the repositoryen


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