Synthesis and evaluation of a novel BODIPY fluorescent probe targeting integrin αvβ3 for cancer diagnosis

A series of integrin α_vβ₃ targeting BODIPY-RGD conjugate were designed and synthesized. Their in vitro and in vivo fluorescence imaging behaviors were investigated. The small molecule compound was designed as an optical imaging near-infrared fluorescent dye which was combined RGD peptide with the meso-amide BODIPYs using succinic moiety as a spacer. The construction alleviated the traditional BODIPY problems including poor water solubility, aggregate caused quench (ACQ) effect, low biocompatibility, etc. In cellular research, BDP-RGD-2 showed rapid, selective uptake in 3 highly expressing integrin α_vβ₃ cell lines MDA-MB-231, A549, U87MG at different extent rather than an integrin α_vβ₃ low level expression cell MCF-7. In animal study, fluorescence imaging of U87MG model targeted by BDP-RGD-2 displayed a highest tumor uptake level and T/N ratio up to 6 h after tail-intravenous injection, which demonstrated BDP-RGD-2 was a promising probe for tracing integrin α_vβ₃ overexpressing tumors.