Advancing Tumor Microenvironment Analysis: A Fluorescence Nanosystem for Caspase-1 Monitoring and Synergistic Therapy.

The lack of precise, real-time analytical tools for monitoring tumor microenvironment changes during treatment hinders advancements in integrated diagnostic and therapeutic platforms. Traditional caspase-3 monitoring strategies are limited by their inability to address drug resistance and newly discovered apoptotic pathways, leading to reduced accuracy and practicality. To overcome these limitations, we developed a fluorescence-based "Trojan horse" nanosystem, PFpR@CM, featuring high-sensitivity Caspase-1 detection, tumor-targeted delivery, and photothermal therapy. Caspase-1 was selected as a biomarker due to its ability to provide accurate feedback on reactive oxygen species (ROS) generation. The system employs Fe-doped polydopamine nanoparticles and red fluorescent carbon quantum dots (RCQDs) as the analytical core, achieving a detection limit of 0.024 U/mL for Caspase-1 with a linear range of 0.05-1.0 U/mL. By integrating MG-63 cell membrane camouflage, PFpR@CM ensures tumor specificity and immune evasion, allowing precise in situ monitoring of ROS production during ferroptosis. Experimental results demonstrate that the system enables simultaneous real-time fluorescence tracking and localized therapeutic interventions, achieving over 80% tumor volume reduction in vivo with minimal systemic toxicity. This work establishes a novel analytical chemistry approach for multifunctional tumor monitoring and treatment, providing an innovative solution to challenges in precision oncology.