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Journal of Biomedical Optics

High payload delivery of optical imaging and photodynamic therapy agents to tumors using phthalocyanine-reconstituted low-density lipoprotein nanoparticles
Author(s): Hui Li; Diane Marotta; Soungkyoo Kim; Theresa M. Busch; E. Paul Wileyto; Gang Zheng
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Paper Abstract

To improve the labeling efficiency of a low-density lipoprotein (LDL)-based photosensitizer (PS) for achieving high probe to protein payload, a tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions, SiPcBOA, is designed and synthesized. Using this novel strategy, SiPcBOA reconstituted LDL (r-SiPcBOA-LDL) with a very high payload (SiPcBOA to LDL molar ratio >3000 to 35001:1) is obtained. Using electron microscopy, we find reconstituted LDL (rLDL) with such a high payload essentially retains the mean particle size of native LDL. Since acetylated LDL binds to scavenger receptors of endothelial and microglial cells instead of LDLR, SiPcBOA reconstituted acetylated LDL (r-SiPcBOA-AcLDL) is also prepared to serve as a negative control to validate the LDL receptor (LDLR) targeting specificity. Confocal microscopy studies demonstrate that the internalization of r-SiPcBOA-LDL by human hepatoblastoma G2 (HepG2) tumor cells is mediated by LDLR pathway. The in vitro photodynamic therapy (PDT) response of HepG2 cells to r-SiPcBOA-LDL is compared to SiPcBOA (free drug control) using a clonogenic assay. The slopes of the linear regression fit to the logarithmic data for these two plots are significantly different from each other (p=0.0007), indicating greatly enhanced efficacy of LDLR-targeted PDT.

Paper Details

Date Published: 1 July 2005
PDF: 7 pages
J. Biomed. Opt. 10(4) 041203 doi: 10.1117/1.2011429
Published in: Journal of Biomedical Optics Volume 10, Issue 4
Show Author Affiliations
Hui Li, Univ. of Pennsylvania (United States)
Diane Marotta, Univ. of Pennsylvania (United States)
Soungkyoo Kim, Univ. of Pennsylvania (United States)
Theresa M. Busch, Univ. of Pennsylvania (United States)
E. Paul Wileyto, Univ. of Pennsylvania (United States)
Gang Zheng, Univ. of Pennsylvania (United States)


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