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1 July 2005 High payload delivery of optical imaging and photodynamic therapy agents to tumors using phthalocyanine-reconstituted low-density lipoprotein nanoparticles
Hui Li, Diane Marotta, Soungkyoo Kim, Theresa M. Busch, E. Paul Wileyto, Gang Zheng
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Journal of Biomedical Optics, Vol. 10, Issue 4, 041203 (July 2005). https://doi.org/10.1117/1.2011429
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.
©(2005) Society of Photo-Optical Instrumentation Engineers (SPIE)
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Hui Li, Diane Marotta, Soungkyoo Kim, Theresa M. Busch, E. Paul Wileyto, and Gang Zheng "High payload delivery of optical imaging and photodynamic therapy agents to tumors using phthalocyanine-reconstituted low-density lipoprotein nanoparticles," Journal of Biomedical Optics 10(4), 041203 (1 July 2005). https://doi.org/10.1117/1.2011429
Published: 1 July 2005
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KEYWORDS
Photodynamic therapy
Proteins
Tumors
Particles
Confocal microscopy
Optical imaging
Picosecond phenomena
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