The use of fluorescent nanoparticles loaded with organic light-emitting dyes are expected to transform live-animal imaging technologies because they are optically stable and nontoxic. In addition, they can be easily modified with functional groups, making them suitable when targeting specific tissues. However, traditional dyes aggregate and lose their emission intensity when incorporated into nanoparticles at high concentrations. In response, researchers at the A*STAR Institute of Materials Research and Engineering (Singapore) have designed a family of dyes with enhanced fluorescence upon aggregation.
Traditional dyes consist of a planar chromophore known as triphenylamine-modified dicyanomethylene, which emits red light in dilute solutions but fluoresces weakly when aggregated. The A*STAR team, led by Bin Liu and Ben Zhong Tang, reversed this phenomenon by attaching propeller-shaped tetraphenylethene pendants to each extremity of the chromophore. Contrary to planar compounds, the shape of the propellers prevents strong stacking interactions between chromophores, blocking the aggregation-caused quenching process. The physical confinement also prevents these propellers from rotating freely, enabling light emission.
The team formulated the dyes using a bovine serum albumin (BSA) matrix — a biocompatible and clinically used polymer — and evaluated their performance as probes. Experimental characterization showed that the wavelength of the emission maximum of the nanoparticles remained unchanged upon encapsulation, and that the intensity of the emitted light increased with the dye loading.
Live imaging of breast cancer cells revealed that the nanoparticles displayed more intense and homogeneously distributed red fluorescence in the cytoplasms than free aggregates, suggesting that BSA boosted the cellular uptake of the dyes. The team also found that the nanoparticles were optically stable in biological media and displayed good biocompatibility.
The researchers intravenously injected the nanoparticles in liver-tumor-bearing mice for in vivo imaging studies. They found that unlike free aggregates, the nanoparticles selectively accumulated in the tumor, clearly highlighting the cancerous tissue in the animals. “This demonstration underscores new research opportunities to explore similar diagnostic probes with potential clinical applications,” Liu remarks.
The team is currently investigating near-infrared emissive biological probes for targeted in vivo tumor imaging applications. The nanoparticles can also be utilized to understand cancer metastasis or the fate of transplanted stem cells. “These probes are promising in multimodal imaging applications through integration with magnetic resonance imaging or nuclear imaging reagents,” Liu says.
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