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D-Cys-D-Asp-Gly-HCit-Gly-Pro-Gln-D-Cys-Ebes-Lys-polyethylene glycol-cholic acids-Cy5.5 telodendrimer nanoparticles.


Leung K1.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2012 Jun 01 [updated 2012 Sep 07].

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National Center for Biotechnology Information, NLM, NIH


Integrins are a family of cell-surface heterodimeric glycoproteins that mediate diverse biological events involving cell–cell and cell–matrix interactions (1). They consist of an α and a β subunit. They are important for cell adhesion and signal transduction. The α3β1 integrin plays an important role in normal lung, kidney, cerebral cortical, and epithelial development (2). On the other hand, it affects tumor growth, tumor invasiveness, and metastasis as the α3β1 integrin is strongly expressed on tumor cells (3, 4). D-Cys-D-Asp-Gly-HCit-Gly-Pro-Gln-D-Cys (OA02) was identified to bind to the α3 integrin on human ovarian cancer cells using one-bead-one-compound combinatorial libraries (5, 6). OA02 was conjugated with Cy5.5 to study in vivo biodistribution of the tracer in tumor-bearing mice (7). Cy5.5 is a NIR fluorescent dye with an absorbance maximum at 675 nm and emission maximum at 694 nm with a high extinction coefficient of 250,000 (mol/L)-1cm-1. OA02-Cy5.5 was found to have a high specific accumulation in α3β1-positve ES-2 human ovarian tumor cells in nude mice. Polymeric micelles compose of a core-shell structure formed by amphiphilic block copolymers (telodendrimers) with nanoparticle sizes of 20-60 nm (8). Ligands and labels can be conjugated to the shell surface and drugs can be encapsulated inside the core of micelles. Xiao et al. (9) conjugated OA02 to micelles comprising linear copolymers of polyethylene glycol (PEG) and cholic acids (CA). Cy5.5 was conjugated to the amino group of the proximal Lys between PEG and cholic acid (CA) to form D-Cys-D-Asp-Gly-HCit-Gly-Pro-Gln-D-Cys-Ebes-Lys- PEG5k-CA8-Cy5.5 telodendrimer nanoparticles (OA02-PEG5k-CA8-Cy5.5 NPs) for in vivo near-infrared (NIR) fluorescence imaging of α3-expressing SKOV-3 human ovarian tumor xenografts in nude mice.

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