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Gas Empowered Dual-Cascade Strategy for Augmented Single-Atom Nanotherapies
Yong Liu1, Xiao-Qiong Li1, Qiao Yu1
1State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Advanced Healthcare Materials
|December 2, 2024
Summary
This study introduces a novel dual-cascade therapy using Fe single-atom nanozymes (SAzymes) that enhances cancer treatment. The strategy boosts enzymatic therapy and mild photothermal therapy by managing hydrogen sulfide and hydroxyl radicals for improved antitumor efficacy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Single-atom nanozymes (SAzymes) show promise in cancer therapy but face challenges like limited enzyme substrates and heat shock protein (HSP) upregulation.
- Concurrent management of these factors is crucial for optimizing SAzyme efficacy.
Purpose of the Study:
- To develop a gas-empowered dual-cascade synergistic strategy for enhancing SAzyme-based enzymatic therapeutics and mild photothermal therapy (PTT).
- To investigate the combined effects of hydrogen sulfide (H2S), hydroxyl radicals (·OH), and mitochondrial dysfunction on cancer treatment.
Main Methods:
- Fe single-atom nanozyme (Fe/SAzyme) loaded with a hydrogen sulfide (H2S) donor (NaHS) was synthesized.
- The strategy involved H2S-mediated catalase suppression for H2O2 conservation, boosting ·OH production for enzymatic therapy.
- ·OH-induced mitochondrial dysfunction was utilized to hinder HSP overexpression and enhance mild PTT.
Main Results:
- The dual-cascade strategy successfully conserved intracellular H2O2, increasing ·OH production for augmented enzymatic therapy.
- Mitochondrial dysfunction was induced, leading to energy remodeling and reduced HSP levels, enhancing mild PTT.
- In vitro and in vivo studies demonstrated significant antitumor efficacy through the synergistic effects of H2S, ·OH, and mild PTT.
Conclusions:
- The developed gas-triggered dual-cascade strategy effectively combines enzymatic therapeutics and mild PTT for enhanced cancer treatment.
- This approach offers a novel pathway for gas-facilitated mild PTT and a valuable paradigm for multimodal synergistic tumor therapy.
