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Published on: December 1, 2016
Lysosome-Targeted D-π-A Near-Infrared Photosensitizer With Dual Type-I/Type-II ROS Generation for Hypoxia-Resilient
Yongfei Huang1, Li Zhang1, Zhefeng Fan1
1School of Chemistry and Chemical Engineering, Shanxi Normal University, TaiYuan, China.
Advanced Healthcare Materials
|August 4, 2026
Summary
This study introduces Lyso-IsTp, a novel photosensitizer for photodynamic therapy (PDT). This targeted approach enhances tumor cell killing by generating multiple reactive oxygen species (ROS) and overcoming tumor hypoxia.
Area of Science:
- Biochemistry
- Materials Science
- Oncology
Background:
- Photodynamic therapy (PDT) efficacy is limited by conventional photosensitizers' single reaction pathway, poor targeting, and poor performance in hypoxic tumors.
- Developing novel photosensitizers with enhanced properties is crucial for improving PDT clinical outcomes.
Purpose of the Study:
- To design and synthesize a lysosome-targeted, near-infrared (NIR) photosensitizer (PS) with dual reactive oxygen species (ROS) generation capabilities.
- To evaluate the efficacy of the novel PS in vitro and in vivo for antitumor applications, particularly in hypoxic conditions.
Main Methods:
- Synthesis of a D-π-A type NIR PS (Lyso-IsTp) incorporating a lysosome-targeting moiety.
- Characterization of photophysical properties, including fluorescence emission, photostability, and ROS generation (Type-I and Type-II) under irradiation.
- In vitro studies using HeLa cells for lysosome targeting confirmation (confocal imaging) and phototoxicity assessment.
- In vivo studies on tumor-bearing nude mice to evaluate antitumor efficacy and biosafety.
Main Results:
- Lyso-IsTp exhibits fluorescence at 750 nm, good photostability, and dual ROS production (•OH, O2⁻•, and ¹O2) under 660 nm irradiation.
- Excellent lysosome targeting in HeLa cells (Pearson coefficient = 0.97) with negligible dark toxicity and significant phototoxicity, inducing apoptosis via ROS-mediated lysosomal damage.
- In vivo studies demonstrated significant tumor growth inhibition and necrosis in Lyso-IsTp-mediated PDT, with no observed systemic toxicity or organ damage.
Conclusions:
- Lyso-IsTp is a high-performance, lysosome-targeted NIR PS with dual ROS generation, offering a promising strategy for hypoxia-tolerant and organelle-specific antitumor PDT.
- The developed PS overcomes limitations of conventional photosensitizers, showing potential for enhanced clinical efficacy in cancer treatment.
