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Multiresponsive solvatochromic fluorophores as viscosity and polarity sensors in solid and liquid state: Lipid droplet sensing in live cell imaging
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DOI：10.1016/j.saa.2026.127797.png)
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Abstract
En 中文
Maintaining a healthy cellular microenvironment, characterized by optimal polarity, viscosity, pH, and temperature, is critical for normal physiological function. Disruptions in these parameters are often associated with disease onset, oxidative stress, as well as metabolic disorders. Fluorescent molecular probes capable of simultaneously monitoring multiple environmental factors offer powerful tools for understanding cellular dynamics. In this context, the design of multiresponsive solvatochromic probes is particularly attractive for real-time, noninvasive tracking of microenvironmental changes in live-cell systems. In this study, we report the development of three D-pi-A type fluorescent probes, DMQN-1, DMQN-2, and DMQN-3, exhibiting distinct responses to environmental polarity and viscosity. Among them, DMQN-2 displays near-infrared emission and pronounced polarity sensitivity, while DMQN-1 and DMQN-3 demonstrate strong viscosity-dependent fluorescence enhancement. Among the three, DMQN-1 demonstrated the highest viscosity sensitivity, with a 202-fold enhancement in fluorescence intensity at 750 nm, followed by DMQN-2 (25-fold at 715 nm) and DMQN-3 (13.5-fold at 640 nm). In polarity-sensitive studies, DMQN-2 showed a significant red shift in emission maximum from 463 nm in cyclohexane to 605 nm in ethanol, with a slope of 4.7, whereas DMQN-1 and DMQN-3 exhibited no linear correlation. Leveraging DMQN-2's polarity sensitivity, we successfully visualized lipid droplets (LDs) in HeLa cells. Pre-incubation with oleic acid, known to increase LD formation, further amplified the fluorescence signal. The LD-targeting capability of DMQN-2 was confirmed through co-localization with commercial LDspecific dyes. Additionally, we synthesized SiO2@DMQN-2 nanoparticles, which exhibited solvent-dependent fluorescence coloration, further highlighting the probe's versatility. We believe the multi-modal responsiveness and strong in vivo imaging potential of these probes, particularly DMQN-2, make them promising tools for sensitive diagnostics, biomarker tracking, and real-time therapeutic monitoring. Its applicability from solution studies to live-cell demonstrates broad utility in diagnostic imaging, microenvironmental mapping, and therapeutic monitoring, advancing the development of intelligent molecular tools for biomedical research.
Keywords:
Microenvironment
Polarity
Solvatochromism
Biomarkers
Lipid droplets
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