Intraoperative tumor mapping using pyridine-carbazole based multifunctional fluorescent probes for precise resection and photodynamic therapeutics

Precise intraoperative tumor localization plays a pivotal role in the quest for refined cancer therapeutics. Addressing this, we have developed a series of novel pyridine-carbazole-based probes (Mito-Pyca1 similar to MitoPyca4) featuring viscosity-enhanced fluorescence and multiphoton absorption properties. Among them, MitoPyca4 showcases significant promise for two-photon activated photodynamic therapy. When subjected to near-infrared irradiation, it reliably produces copious singlet oxygen, crucial for targeted tumor treatment. In vitro and in vivo experiments validated the capacity of Mito-Pyca4 to effectively induce cell apoptosis and impede tumor growth with minimal toxicity, positioning it as a potential candidate for photodynamic therapy. Furthermore, the specificity of Mito-Pyca4 for cancer cells was confirmed in co-culture experiments, and the probe was utilized for in vivo fluorescence-guided surgery. Successfully distinguishing tumor tissue from normal tissue, Mito-Pyca4 facilitates precise tumor resection. In summary, this comprehensive study establishes MitoPyca4 as a versatile tool for nonlinear optical imaging, viscosity sensing, and fluorescence-guided cancer surgery and treatment, providing surgeons an unparalleled advantage in discerning tumor margins. Through this research, we underscore the transformative potential of integrating chemical innovation with surgical and therapeutic techniques.