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Published on: August 30, 2017
Sequential H2S-Triggered Redox Relay Nanoprobes for Self-Sustained Chem-Illuminating Cascade Photodynamic Therapy
Jing Yang1, Yao Lu1, Yutao Zhang1
1Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Shanghai Key Laboratory of Functional Materials Chemistry, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center For Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, China.
This study introduces NP-Rubine, a novel nano-photosensitizer for chemiluminescence-driven photodynamic therapy (CL-PDT). It overcomes the "redox paradox" by using hydrogen sulfide (H2S) to generate singlet oxygen and deplete reductants, enhancing tumor treatment.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Cancer Therapy
Background:
- Endogenous chemiluminescence (CL) offers advantages for photodynamic therapy (PDT) by enabling light-independent, tumor-specific activation.
- Current CL-PDT systems often rely on intracellular oxidants, creating a "redox paradox" that counteracts the goal of increasing oxidative stress in tumors.
Purpose of the Study:
- To develop a novel nano-photosensitizer, NP-Rubine, that addresses the "redox paradox" in CL-PDT.
- To decouple photon generation from oxidant consumption for enhanced therapeutic outcomes.
Main Methods:
- Designed NP-Rubine, a sequential hydrogen sulfide (H2S)-triggered redox relay nano-photosensitizer.
- Utilized Rubine (chemiluminescent probe) and OPDEA-Ppa (N-oxide scaffold) for H2S responsiveness and singlet oxygen (1O2) production via chemiluminescence resonance energy transfer (CRET).
- Investigated N-oxide moiety for enhanced tumor penetration and depletion of intracellular NADPH.
Main Results:
- NP-Rubine selectively activated by endogenous H2S to produce 1O2.
- Demonstrated deep-tissue imaging and potent antitumor efficacy in HCT116 xenografts.
- Synergistically amplified intracellular redox imbalance by coupling oxidant generation with reductant exhaustion.
Conclusions:
- NP-Rubine represents a bio-reductant, self-sustained targeted CL-PDT strategy.
- This approach circumvents limitations of oxidation-fueled CL-PDT systems.
- Offers a robust benchmark for precision nanomedicine in complex redox environments.
