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Naphthalocyanine-reconstituted LDL nanoparticles for in vivo cancer imaging and treatment

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Authors: Liping Song, Hui Li, Ulas Sunar, Juan Chen, Ian Corbin

Published Date January 2007 Volume 2007:2(4) Pages 767 - 774
DOI: http://dx.doi.org/10.2147/IJN.S

Liping Song1,2, Hui Li2, Ulas Sunar3, Juan Chen2,4, Ian Corbin2,4, Arjun G Yodh3, Gang Zheng2,4

1Department of Chemistry, Shanghai University, China; 2Department of Radiology and 3Department of Physics and Astronomy, University of Pennsylvania, USA; 4Department of Medical Biophysics, University of Toronto, Ontario, Canada; Division of Biophysics and Bioimaging, Ontario Cancer Institute, Canada

Abstract: Low density lipoproteins (LDLs) are naturally occurring nanoparticles that are biocompatible, biodegradable and non-immunogenic. Moreover, the size of LDL particle is precisely controlled (∼22 nm) by its apoB-100 component, setting them apart from liposomes and lipid micelles. LDL particles have long been proposed as a nanocarrier for targeted delivery of diagnostics and therapeutics to LDL receptor (LDLR)-positive cancers. Here, we report the design and synthesis of a novel naphthalocyanine (Nc)-based photodynamic therapy (PDT) agent, SiNcBOA, and describe its efficient reconstitution into LDL core (100:1 payload). Possessing a near-infrared (NIR) absorption wavelength (>800 nm) and extremely high extinction coefficient (>105 M–1cm–1), SiNcBOA holds the promise of treating deeply seated tumors. Reconstituted LDL particles (r-Nc-LDL) maintain the size and shape of native LDL as determined by transmission electron microscopy, and also retain their LDLR-mediated uptake by cancer cells as demonstrated by confocal microscopy. Its preferential uptake by tumor vs normal tissue was confirmed in vivo by noninvasive optical imaging technique, demonstrating the feasibility of using this nanoparticle for NIR imaging-guided PDT of cancer.

Keywords: naphthalocyanine, lipoproteins, photodynamic therapy, near-infrared optical imaging, nanoparticle, drug delivery








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