Biocompatible Nanoparticles with Aggregation‐Induced Emission Characteristics as Far‐Red/Near‐Infrared Fluorescent Bioprobes for In Vitro and In Vivo Imaging Applications

TLDR

Light emission of the TPA‑DCM fluorogen is quenched by aggregation, limiting its utility in bioimaging. By attaching tetraphenylethene termini to TPA‑DCM, the authors created an aggregation‑induced emission fluorogen (TPE‑TPA‑DCM) that, when formulated with bovine serum albumin, forms uniformly sized, bright, low‑toxic protein nanoparticles. The TPE‑TPA‑DCM/BSA nanoparticles were successfully used for far‑red/near‑infrared imaging of MCF‑7 breast‑cancer cells in vitro and of hepatoma‑22 tumors in mice, exhibiting high cancer‑cell uptake and tumor‑targeting via the enhanced permeability and retention effect.

Abstract

Abstract Light emission of 2‐(2,6‐bis(( E )‐4‐(diphenylamino)styryl)‐4 H ‐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)‐4 H ‐pyran‐4‐ylidene)malononitrile (TPE‐TPA‐DCM), is more emissive in the aggregate state, showing the 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 (H 22 )‐tumor‐bearing mouse model, respectively. The AIE‐active fluorogen‐loaded BSA NPs show an excellent cancer cell uptake and a prominent tumor‐targeting ability in vivo due to the enhanced permeability and retention effect.