Far-red/near-infrared fluorescent bioprobes based on biocompatible nanoparticles with aggregation-induced emission characteristics for bioimaging applications

Light emission of 2-(2,6-bis((E)-4-(diphenylamino)styryl]-4H-pyran-4-ylidene}malononitrile (TPA-DCM) is weakened by aggregate formation. Attaching tetraphenylethene (TPE) units as terminals to TPA-DCM dramatically changes its emission behavior: the resulting fluorogen 2-(2,6-bis((E)-4-(phenyl(4’-(1,2,2-triphenylvinyl)-[1,1’-biphenyl]-4- yl)amino)styryl)-4H-pyran-4-ylidene)malononitrile (TPE-TPA-DCM) is more emissive in the aggregate state, showing a novel phenomenon of aggregation-induced emission (AIE). Formulation of TPE-TPA-DCM using bovine serum albumin (BSA) as the polymer matrix yields uniformly sized protein nanoparticles (NPs) with high brightness and low cytotoxicity. Applications of the fluorogen-loaded BSA NPs for in vitro and in vivo far-red/near-infrared (FR/NIR) bioimaging are successfully demonstrated using MCF-7 breast cancer cells and a murine hepatoma-22 (H₂₂) tumorbearing mice model, respectively. The AIE-active fluorogen-loaded BSA NPs show excellent cancer cell uptake and prominent tumor targeting ability in vivo due to the enhanced permeability and retention effect.