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Functional coating of liposomes using a folate–polymer conjugate to target folate receptors

Authors Watanabe K, Kaneko M, Maitani Y

Received 11 April 2012

Accepted for publication 14 May 2012

Published 13 July 2012 Volume 2012:7 Pages 3679—3688

DOI https://doi.org/10.2147/IJN.S32853

Review by Single-blind

Peer reviewer comments 2

Kazuo Watanabe, Makoto Kaneko, Yoshie Maitani

Institute of Medical Chemistry, Hoshi University, Tokyo, Japan

Abstract: Folate-polymer-coated liposomes were developed for targeted chemotherapy using doxorubicin (DXR) as a model drug. Folate-poly(L-lysine) (F–PLL) conjugates with a folate modification degree of 16.7 mol% on epsilon amino groups of PLL were synthesized. DXR-loaded anionic liposomes were coated with F–PLL, and the cellular association of F–PLL-coated liposomes was evaluated by flow cytometry, and confocal microscopy in human nasopharyngeal carcinoma KB cells overexpressing folate receptors (FRs), and human lung adenocarcinoma A549 cells [FR (-)]. The existence of a polymer layer on the surface of F–PLL-coated liposomes was confirmed by zeta potential analysis. The KB cellular association of F–PLL-coated liposomal DXR was increased compared with that of PLL-coated liposomes and was inhibited in the presence of free folic acid. Twofold higher cytotoxicity of F–PLL-coated liposomal DXR was observed compared with that of the PLL-coated liposomal DXR in KB cells, but not in A549 cells, suggesting the presence of FR-mediated endocytosis. These results indicated that folate-targeted liposomes were prepared successfully by coating the folate–polymer conjugate F–PLL. This novel preparation method of folate-targeted liposomes is expected to provide a powerful tool for the development of a folate-targeting drug nanodevice as coating with ligand–polymer conjugates can be applicable to many kinds of particles, as well as to lipid-based particles.

Keywords: cellular association, folate-targeting, liposome, poly-L-lysine, polymer coating, tumor targeting

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