Development Of A Squaraine-Based Molecular Probe For Dual-Modal In Vivo Fluorescence And Photoacoustic Imaging
BIOCONJUGATE CHEMISTRY(2020)
摘要
Dual-modular imaging approaches combining near-infrared (NIR) fluorescence (FLI) and photoacoustic imaging (PAI) require suitable contrast agents to produce dual-modular signals. Although nanoparticles have been used to develop PAI agents, small molecule-based imaging agents have not been extensively studied, highlighting the need to design new fluorophores with an enhanced multifunctional ability. Thus, in this study, we designed a novel squaraine (SQ)-based dye and reported its rational preparation and conjugation with a cancer targeting peptide. Specifically, benzoindole-derived SQ (BSQ) showed strong absorption and fluorescence properties at above 650 nm under aqueous conditions, with a maximum absorption and emission at 665 and 680 nm, respectively. Moreover, PA signal scanning experiments revealed a maximum signal intensity in the range 680-700 nm. BSQ was also conjugated with cyclic arginine-glycine-aspartic acid (cRGD) to improve its active targeting ability for the alpha(v)beta(3) integrin, which is overexpressed in various cancer and angiogenic cells. A series of in vitro, in vivo, and ex vivo FLI studies showed that the cRGD conjugated BSQ (BSQ-RGD(2)) successfully stained and targeted alpha(v)beta(3) integrin-overexpressing tumor cells and xenografts, which were clearly visualized by FLI and PAI. Therefore, BSQ-RGD(2) can successfully be applied to dual-modular imaging of the specific biomarker in living animals.
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