Triphenylquinoline (TPQ)-Based Dual-State Emissive Probe for Cell Imaging in Multicellular Tumor Spheroids

Insufficient intratumoral penetration and limited stroma distribution of the imaging probes or theranostics can lead to a poor-quality diagnosis or therapeutic resistance. Multicellular tumor spheroids can recapitulate the physiological environment of tumor tissues with the extracellular matrix and is thus a better in vitro tumor model to evaluate the imaging performance and barrier penetration capability of advanced cancer imaging probes. In this Article, we designed and synthesized a series of quinoline-based fluorophores with strong emissions in both solution and solid states. The quinoline core can be constructed via a one-pot iron-catalysis reaction. Optical properties and single crystal structures of these quinoline derivatives were tuned by varying the substitutes at the 6-position of the quinoline core. The twisted intramolecular charge transfer effect can enhance the fluorescent efficiency, resulting in the high quantum yield of TPQ-TPA in both solution (70%) and solid (48%) states (TPQ, triphenylquinoline; TPA, triphenylamine). In addition, TPQ-TPA exhibited a good biocompatibility and can deeply penetrate into 3D tumor spheroids within 12 h. The results indicated that quinoline can be a new fluorescent scaffold, and the employment of quinoline-based probes will provide a new platform for biological applications.