Increasing the antitumor efficacy of doxorubicin-loaded liposomes with peptides anchored via a chelator lipid

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dc.contributor.authorHerringson, Thomas
dc.contributor.authorAltin, Joseph
dc.date.accessioned2015-12-10T22:16:20Z
dc.date.issued2011
dc.date.updated2016-02-24T11:41:32Z
dc.description.abstractThe therapeutic efficacy of anticancer drugs like doxorubicin can be significantly increased by their incorporation into liposomes, but an ability to actively target the drug-containing liposomes to tumors could well provide an even greater curative effect. In this work, a commercial preparation of doxorubicin-loaded liposomes (Caelyx) was modified by incorporation of the metal chelator lipid 3(nitrilotriacetic acid)-ditetradecylamine (NTA3-DTDA) to enable engraftment of histidine-tagged targeting molecules. Our results show that when engrafted with p15-RGR, a His-tagged peptide containing a sequence purported to bind platelet-derived growth factor receptor β (PDGFRβ), NTA3-DTDA-containing Caelyx (3NTA-Caelyx) can be targeted to NIH-3T3 cells in vitro, leading to increased cytotoxicity compared with non-targeted 3NTA-Caelyx. PDGFRβ is known to be expressed on pericytes in the tumor vasculature; however, when radiolabeled p15-RGR liposomes were administered to mice bearing subcutaneous B16-F1 tumors, minimal accumulation into tumors was observed. In contrast, an alternative targeting peptide, p46-RGD, was found to actively direct liposomes to tumors (4.7 %ID/g). Importantly, when injected into tumor-bearing mice, p46-RGD-engrafted 3NTA-Caelyx significantly decreased the tumor growth rate compared with controls. These results indicate that the incorporation of NTA3-DTDA into liposomal drugs could represent a simple modification to the drug to allow engraftment of targeting molecules and to increase its efficacy.
dc.identifier.issn1061-186X
dc.identifier.urihttp://hdl.handle.net/1885/50890
dc.publisherInforma Healthcare
dc.sourceJournal of Drug Targeting
dc.subjectKeywords: 3 (nitrilotriacetic acid)ditetradecylamine; chelating agent; doxorubicin; liposome; platelet derived growth factor beta receptor; unclassified drug; animal experiment; animal model; antineoplastic activity; article; cell strain 3T3; controlled study; cyto Caelyx; Chelator lipid; Long-circulating liposomes; Nanoparticles; Tumor targeting
dc.titleIncreasing the antitumor efficacy of doxorubicin-loaded liposomes with peptides anchored via a chelator lipid
dc.typeJournal article
local.bibliographicCitation.lastpage9
local.bibliographicCitation.startpage1
local.contributor.affiliationHerringson, Thomas, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationAltin, Joseph, College of Medicine, Biology and Environment, ANU
local.contributor.authoremailu4235798@anu.edu.au
local.contributor.authoruidHerringson, Thomas, u2557015
local.contributor.authoruidAltin, Joseph, u4235798
local.description.embargo2037-12-31
local.description.notesImported from ARIES
local.identifier.absfor111205 - Chemotherapy
local.identifier.absseo920102 - Cancer and Related Disorders
local.identifier.ariespublicationu8611701xPUB212
local.identifier.citationvolumeearly online
local.identifier.doi10.3109/1061186X.2010.536984
local.identifier.scopusID2-s2.0-80051762063
local.identifier.thomsonID000293743800011
local.identifier.uidSubmittedByu8611701
local.type.statusPublished Version

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