Intracellular fluorogenic supramolecular assemblies for self-reporting bioorthogonal prodrug activation
Yan Zhao1,2, Qingxin Yao1,2, Jiali Chen1,2
1CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China. gaoy@nanoctr.cn.
Biomaterials Science
|August 23, 2022
Summary
This study introduces a visual drug delivery system (VDDS) that uses fluorescence to track bioorthogonal prodrug activation. The system allows real-time monitoring of drug release and efficacy in cells.
Area of Science:
- Biomedical Engineering
- Drug Delivery Systems
- Molecular Imaging
Background:
- Precision medicine requires visualizable drug delivery systems (DDS).
- Bioorthogonal prodrug activation enhances therapeutic index by reducing side effects.
- Current methods lack real-time monitoring of bioorthogonal activation events.
Purpose of the Study:
- To develop a self-reporting bioorthogonal prodrug activation system using fluorescence.
- To enable visualization and quantification of prodrug activation events.
- To correlate drug release with cellular response.
Main Methods:
- Constructed ROS-instructed supramolecular assemblies with tetrazine as a quencher and activator.
- Utilized inverse-electron-demand Diels-Alder (IEDDA) reaction for simultaneous fluorescence and drug release.
- Demonstrated selective assembly in tumor cells and cell spheroids based on redox status.
Main Results:
- Achieved a linear relationship between fluorescence emission and active drug liberation.
- Showcased fluorescence brightness correlating with drug release and cell survival rate.
- Validated the system's ability to visualize prodrug activation in complex cellular models.
Conclusions:
- Developed a fluorescence-based visualizable DDS (VDDS) for bioorthogonal prodrug activation.
- The VDDS allows elucidation of multi-step drug delivery processes.
- This system provides a tool for determining prodrug activation efficacy in real-time.
