CO₂-Responsive Water-Soluble Conjugated Polymers as a Multifunctional Fluorescent Probe for Bioimaging Applications

We describe important progress in the synthesis and development of gas-responsive water-soluble conjugated polymers (WSCPs) with potential as multifunctional fluorescent materials for biomedical imaging and probes. A water-soluble WSCP (I-PT) composed of a hydrophobic fluorescent polythiophene backbone and a hydrophilic imidazole side chain was successfully prepared through a facile and efficient two-step synthetic route. Owing to the repulsive force between the hydrophilic and hydrophobic segments and the highly sensitive carbon dioxide (CO₂)- and nitrogen (N₂)-responsive imidazole groups in its structure, I-PT can spontaneously self-assemble into spherical-like nanoparticles in an aqueous environment, and thus exhibits unique light absorption and fluorescence properties as well as rapid responsiveness to CO₂ and N₂. In addition, its structure, optical absorption/fluorescence behavior, and surface potential can be quickly turned on and off through alternating cycles of CO₂ and N₂ bubbling and exhibit controllable cyclic switching stability, thereby allowing effective manipulation of its hierarchical structure and chemical-physical characteristics. More importantly, a series of in vitro cell experiments confirmed that, compared to the significant cytotoxicity of pristine and N₂-treated I-PT nanoparticles, CO₂-treated I-PT nanoparticles exhibit extremely low cytotoxicity in normal and cancer cells and undergo greatly accelerated cellular uptake, resulting in a significant increase in the intensity and stability of their fluorescence signal in the intracellular environment. Overall, this newly discovered CO₂/N₂-responsive system provides new insights to effectively enhance the biocompatibility, cellular internalization, and intracellular fluorescence characteristics of WSCPs and holds great potential for biomedical imaging/sensing applications.