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Published on: June 13, 2014
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Self-Reported 2D Metal-Organic Nanosheet Pre-Catalyst for Bioorthogonally Anti-Tumor Immunotherapy
Xue Zhai1, Hao Su1, Yuxuan Tu1
1State Key Laboratory of Organic Electronics and Information Displays, Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing, China.
Advanced Healthcare Materials
|November 30, 2025
Summary
This study introduces a self-reporting biopalladium pre-catalyst for bioorthogonal reactions. It activates in tumors, signals optimal drug timing with fluorescence, and enhances immunotherapy for cancer treatment.
Area of Science:
- Bioconjugation Chemistry
- Nanomaterials Science
- Cancer Immunotherapy
Background:
- Transition metal catalysts face challenges in biological settings like instability and toxicity.
- Developing stable and biocompatible catalysts for bioorthogonal reactions is crucial for in vivo applications.
- Existing methods lack real-time monitoring of catalytic activity and optimal drug delivery timing.
Purpose of the Study:
- To design a self-reporting biopalladium pre-catalyst for bioorthogonal reactions in tumor tissues.
- To enable simultaneous catalytic activation and fluorescence signaling for precise drug delivery.
- To evaluate the efficacy of this system in combination with immunotherapy for cancer treatment.
Main Methods:
- Fabrication of ultrathin 2D metal-organic nanosheets (Pd-BDP) as a stable Pd(II) reservoir.
- Activation of Pd-BDP by tri(2-furyl) phosphine (TFP) under physiological conditions.
- Visualization of catalytic activation via near-infrared (NIR) fluorescence from released BDP photosensitizer.
- Combination therapy using the immunotherapeutic prodrug (R848) and photodynamic/photothermal therapy (PDT/PTT)-induced immunogenic cell death (ICD).
Main Results:
- The Pd-BDP pre-catalyst demonstrated good biocompatibility and stability, releasing active palladium species.
- Catalytic activation occurred in situ with a decaging yield of 63.3% under physiological conditions.
- NIR fluorescence provided real-time monitoring of the reaction, indicating optimal timing for prodrug administration.
- Combination therapy significantly inhibited primary tumor growth and lung metastasis in a mouse model, reducing systemic inflammation.
Conclusions:
- The developed self-reporting biopalladium pre-catalyst offers a stable and biocompatible platform for bioorthogonal reactions.
- Simultaneous catalytic activity and fluorescence signaling allow for precise control and monitoring of therapeutic interventions.
- This approach enhances synergistic bioorthogonal immunotherapy, showing potential for improved cancer treatment safety and efficacy.
