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

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 αβ 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 αβ 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 α integrin on human ovarian cancer cells using one-bead-one-compound combinatorial libraries (5, 6). OA02 was conjugated with Cy5.5 to study 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)cm. OA02-Cy5.5 was found to have a high specific accumulation in αβ-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- PEG-CA-Cy5.5 telodendrimer nanoparticles (OA02-PEG-CACy5.5 NPs) for near-infrared (NIR) fluorescence imaging of αexpressing SKOV-3 human ovarian tumor xenografts in nude mice.