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Tumor Site-Specific In Vivo Theranostics Enabled by Microenvironment-Dependent Chemical Transformation and
Yunfei Zuo1, Pei Li1,2, Wen-Jin Wang3
1Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science, State Key Laboratory of Molecular Neuroscience, and Department of Chemical and Biological Engineering, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, P. R. China.
Abstract:
Precise tumor diagnosis and treatment remain complex challenges. While numerous fluorescent probes have been developed for tumor-specific imaging and therapy, few exhibit effective function in vivo. Herein, a probe called TQ-H2 is designed that can realize robust theranostic effects both in vitro and in vivo. In vitro, TQ-H2 specifically targets the lysosome and reacts with hydroxyl radical (·OH) to generate TQ-HA, which lights up the cells. TQ-HA generates reactive oxygen species (ROS) under light irradiation, enabling the simultaneous induction and monitoring of apoptosis and ferroptosis in tumor cells. Remarkably, TQ-HA also acts as a self-amplifier, autocatalytically activating TQ-H2 by generating ·OH under light exposure. This self-amplification aligns with the tumor microenvironment, where TQ-H2 undergoes chemical transformation, distinguishing tumors from healthy tissue via near-infrared (NIR) fluorescence imaging. Furthermore, ROS generated by TQ-HA effectively kills tumor cells and inhibits tumor growth without harming normal cells. This study offers a promising strategy for targeted tumor theranostics using self-amplifying microenvironment-responsive fluorescent probes.
Insights
A novel fluorescent probe, TQ-H2, enables effective in vivo tumor theranostics. It targets lysosomes, generates reactive oxygen species for apoptosis and ferroptosis, and self-amplifies for enhanced tumor imaging and treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Accurate tumor diagnosis and treatment are significant clinical hurdles.
- Existing fluorescent probes often lack effective in vivo performance for tumor theranostics.
Purpose of the Study:
- To design a novel fluorescent probe, TQ-H2, for robust in vitro and in vivo tumor theranostic applications.
- To investigate the probe's mechanism, including lysosomal targeting, reactive oxygen species generation, and self-amplification for enhanced tumor imaging and therapy.
Main Methods:
- Development of the TQ-H2 probe for lysosomal targeting and reaction with hydroxyl radical (·OH).
- In vitro and in vivo evaluation of TQ-H2's ability to generate reactive oxygen species (ROS) under light irradiation.
- Assessment of TQ-H2's self-amplifying mechanism and near-infrared (NIR) fluorescence imaging capabilities in the tumor microenvironment.
- Evaluation of the therapeutic efficacy of ROS generated by TQ-HA in tumor cells and inhibition of tumor growth.
Main Results:
- TQ-H2 specifically targets lysosomes and generates TQ-HA upon reaction with ·OH, enabling cellular visualization.
- TQ-HA induces and monitors apoptosis and ferroptosis in tumor cells via ROS generation under light.
- TQ-HA exhibits a self-amplifying effect, enhancing ·OH production and TQ-H2 activation in the tumor microenvironment.
- TQ-H2 facilitates NIR fluorescence imaging for distinguishing tumors from healthy tissues.
- The generated ROS effectively kill tumor cells and inhibit tumor growth with minimal harm to normal cells.
Conclusions:
- The TQ-H2 probe demonstrates significant potential for in vivo tumor theranostics.
- The self-amplifying and microenvironment-responsive nature of the probe offers a promising strategy for targeted cancer treatment and imaging.
