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Updated: May 23, 2025
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Advancing Tumor Microenvironment Analysis: A Fluorescence Nanosystem for Caspase-1 Monitoring and Synergistic Therapy
Chen Zhao1, Mo Ma1,2, Jukun Yang1
1College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China.
Abstract:
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.
Insights
This study introduces a novel nanosystem for real-time tumor microenvironment monitoring and therapy. It accurately detects Caspase-1, enabling targeted treatment and significant tumor reduction with minimal toxicity.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Current tumor microenvironment monitoring lacks precision and real-time capabilities, hindering integrated diagnostic and therapeutic platforms.
- Traditional methods for monitoring apoptosis, like caspase-3 detection, struggle with drug resistance and new pathways, limiting accuracy and practicality.
Purpose of the Study:
- To develop a novel fluorescence-based nanosystem for high-sensitivity Caspase-1 detection, tumor-targeted delivery, and photothermal therapy.
- To overcome limitations in monitoring tumor microenvironment changes and drug resistance during cancer treatment.
Main Methods:
- Development of a "Trojan horse" nanosystem (PFpR@CM) using Fe-doped polydopamine nanoparticles and red fluorescent carbon quantum dots (RCQDs).
- Incorporation of MG-63 cell membrane camouflage for tumor specificity and immune evasion.
- Utilizing Caspase-1 as a biomarker for reactive oxygen species (ROS) generation and ferroptosis monitoring.
Main Results:
- Achieved a Caspase-1 detection limit of 0.024 U/mL with a linear range of 0.05-1.0 U/mL.
- Demonstrated precise in situ monitoring of ROS production during ferroptosis with real-time fluorescence tracking.
- Achieved over 80% tumor volume reduction in vivo with minimal systemic toxicity.
Conclusions:
- The PFpR@CM nanosystem offers a novel analytical chemistry approach for multifunctional tumor monitoring and treatment.
- This system provides an innovative solution for precision oncology, enabling simultaneous diagnostics and therapeutics.
- The developed system enhances tumor specificity and immune evasion for effective cancer therapy.
