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Modularized GSH-Proton Tandem-Responsive "Off-Brighter" Persistent Luminescent Nano-System for Visualized Synergetic
Chang Yin1, Kai Long1, Xinxin Yuan1
1Key Laboratory of Functional Polymer Materials of the Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, China.
Small (Weinheim an Der Bergstrasse, Germany)
|July 23, 2026
Summary
This study presents a novel "Off-Brighter" persistent luminescence (PersL) theranostic strategy for visualized cancer therapy. This modular nano-agent enhances imaging contrast and achieves 96.2% tumor suppression in preclinical models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Visualized theranostics are crucial for cancer management but face challenges in achieving high contrast, efficacy, and versatility.
- Current theranostic strategies often lack facile design and broad applicability.
Purpose of the Study:
- To develop a novel modular "Off-Brighter" persistent luminescence (PersL) theranostic strategy for visualized cancer therapy.
- To integrate proton-responsive imaging and GSH-responsive synergistic photothermal/chemodynamic therapy modules into a single nano-agent.
Main Methods:
- A modular nano-agent was designed, combining a dye-sensitized proton-responsive PersL imaging module (ZR) and a GSH-responsive synergistic photothermal/chemodynamic therapy module (PAHIR-Fcss) with IR808 and FcSH.
- The "Off-Brighter" activation mechanism was investigated, involving FcSH quenching of PersL and subsequent "GSH-proton" tandem-responsive enhancement.
- Real-time imaging guided the monitoring of drug delivery and determination of optimal combination therapy timing.
Main Results:
- The "Off-Brighter" strategy achieved a 12.3-fold luminescence enhancement and a tumor imaging contrast of 274.95.
- The synergistic photothermal/chemodynamic therapy resulted in 96.2% tumor suppression in murine breast cancer models.
- PersL imaging determined that a single 14-day treatment course optimized therapeutic efficacy while minimizing overtreatment risks.
Conclusions:
- The developed modular "Off-Brighter" PersL theranostic strategy offers a versatile and generalizable platform for visualized cancer therapy.
- The facile modular design allows for interchangeable imaging and therapeutic components, enabling tailored clinical applications.
- This approach significantly improves imaging contrast and therapeutic efficacy for cancer treatment.
