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Proceedings Paper

Phthalocyanine-labeled LDL for tumor imaging and photodynamic therapy
Author(s): Hui Li; Diane Marotta; Soungkyoo Kim; Britton Chance; Jerry D. Glickson; Theresa M. Busch; Gang Zheng
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Paper Abstract

Current limitation of both near-infrared (NIR) tumor imaging and photodynamic therapy (PDT) is their lack of sufficient tumor-to-tissue contrast due to the relatively non-specific nature of delivering dye to the tumor, which has led to false negatives for NIR imaging and inadequate therapeutic ratio for PDT. Hence, agents targeting “cancer signatures”, i.e. molecules that accumulate selectively in cancer cells, are particular attractive. One of these signatures is low-density-lipoprotein receptor (LDLR), which is overexpressed in many tumors. We have developed pyropheophorbide cholesterol oleate reconstituted LDL as a LDLR-targeting photosensitizer (PS) and demonstrated its LDLR-mediated uptake in vitro and in vivo. To improve the labeling efficiency for achieving high probe/protein ratio, tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions, (tBu)4SiPcBOA, was designed and synthesized. This compound was designed to 1) prevent the PS aggregation; 2) improve the PS solubility in non-polar solvent; and 3) maximize the PS binding to LDL phospholipid monolayer. Using this novel strategy, (tBu)4SiPcBOA was reconstituted into LDL (r-SiPcBOA-LDL) with a very high payload (500:1 molar ratio). In addition, (tBu)4SiPcBOA reconstituted acetylated LDL (r-SiPcBOA)-AcLDL with similar payload was also prepared. Since Ac-LDL cannot bind to LDLR, (r-SiPcBOA)-AcLDL can serve as the negative control to evaluate LDLR targeting specificity. For biological evaluation of these new agents, confocal microscopy and in vitro PDT protocols were performed using LDLR-overexpressing human hepatoblastoma G2 (HepG2) tumor model. These studies suggest that LDL serves as a delivery vehicle to bring large amount of the NIR/PDT agents selectively to tumor cells overexpressing LDLR.

Paper Details

Date Published: 18 January 2005
PDF: 8 pages
Proc. SPIE 5630, Optics in Health Care and Biomedical Optics: Diagnostics and Treatment II, (18 January 2005); doi: 10.1117/12.573912
Show Author Affiliations
Hui Li, Univ. of Pennsylvania (United States)
Diane Marotta, Univ. of Pennsylvania (United States)
Soungkyoo Kim, Univ. of Pennsylvania (United States)
Britton Chance, Univ. of Pennsylvania (United States)
Jerry D. Glickson, Univ. of Pennsylvania (United States)
Theresa M. Busch, Univ. of Pennsylvania (United States)
Gang Zheng, Univ. of Pennsylvania (United States)

Published in SPIE Proceedings Vol. 5630:
Optics in Health Care and Biomedical Optics: Diagnostics and Treatment II
Britton Chance; Mingzhe Chen; Arthur E. T. Chiou; Qingming Luo, Editor(s)

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