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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Herringson, Thomas P. Altin, Joseph G.
Description	Country affiliation: Australia Author Affiliation: Herringson TP ( Division of Biomedical Science and Biochemistry, Research School of Biology, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, Australia.)
Abstract	The 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 (NTA(3)-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 ß (PDGFRß), NTA(3)-DTDA-containing Caelyx (3NTA-Caelyx) can be targeted to NIH-3T3 cells in vitro, leading to increased cytotoxicity compared with non-targeted 3NTA-Caelyx. PDGFRß 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 NTA(3)-DTDA into liposomal drugs could represent a simple modification to the drug to allow engraftment of targeting molecules and to increase its efficacy.
File Format	HTM / HTML
ISSN	1061186X
Issue Number	8
Volume Number	19
e-ISSN	10292330
Journal	Journal of Drug Targeting
Language	English
Publisher	Taylor & Francis
Publisher Date	2011-09-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Amines Chemistry Antibiotics, Antineoplastic Therapeutic Use Chelating Agents Doxorubicin Drug Carriers Nitrilotriacetic Acid Analogs & Derivatives Peptide Fragments Animals Administration & Dosage Pharmacokinetics Cell Line, Tumor Cell Survival Drug Effects Dose-response Relationship, Drug Drug Compounding Female Flow Cytometry Melanoma, Experimental Drug Therapy Mice Mice, Inbred C57bl Nih 3t3 Cells Particle Size Tissue Distribution Xenograft Model Antitumor Assays Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science

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