Nanoparticles Selectively Regulate the Generation and Scavenging of Multiple Reactive Oxygen Species at Designated
Xiaojun Cai1,2, Moran Huang3, Wujie Qiu4
1Shanghai Key Laboratory of Neuro-Ultrasound for Diagnosis and Treatment, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P. R. China.
Abstract:
Photodynamic therapy (PDT) is recognized as a promising therapeutic modality for cancer, psoriasis, bacterial infection, atherosclerosis, and other diseases, yet confronts persistent challenges of oxygen dependency, limited diversity of reactive oxygen species (ROS), and collateral photodamage to healthy tissues. Here, we report that unlike traditional PDT, near-infrared-activated Prussian blue nanoparticles (PBs) uniquely interact with hydrogen peroxide (H2O2) to concurrently generate hydroxyl radicals (·OH), hydroperoxyl radicals (·OOH), and singlet oxygen (1O2) through an oxygen-independent pathway, thereby compensating for the damage and selectivity differences between distinct ROS. PB, H2O2, and light are the three essential factors for producing ROS. Furthermore, PBs exhibit the ability to scavenge H2O2, ·OH, and ·OOH, thereby maintaining the redox homeostasis and showing negligible phototoxicity in normal tissues. Intriguingly, light irradiation enables PBs to selectively regulate both generation and scavenging of ROS. PB shows a powerful capability to selectively regulate the generation and scavenging of ROS at the designated location and time. Proof-of-concept validation through an infected wound murine model reveals that PBs' exceptional therapeutic efficacy, achieving unprecedented healing outcomes. The discovery of PB as a special photosensitizer holds promise for enriching the fundamental understanding of PDT, overcoming its inherent limitations, and advancing the development of next-generation PDT strategies.
Insights
Near-infrared-activated Prussian blue nanoparticles (PBs) offer an oxygen-independent photodynamic therapy (PDT) by generating diverse reactive oxygen species (ROS). This novel approach overcomes PDT limitations and shows exceptional healing efficacy in preclinical models.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Photochemistry
Background:
- Photodynamic therapy (PDT) faces challenges including oxygen dependency, limited reactive oxygen species (ROS) diversity, and collateral damage.
- Existing PDT strategies struggle with selectivity and efficacy due to the specific properties of different ROS.
Purpose of the Study:
- To develop a novel photosensitizer for photodynamic therapy (PDT) that overcomes oxygen dependency and generates diverse ROS.
- To investigate the unique ROS generation and scavenging properties of Prussian blue nanoparticles (PBs) under near-infrared light activation.
- To evaluate the therapeutic efficacy of PB-based PDT in a preclinical model.
Main Methods:
- Near-infrared-activated Prussian blue nanoparticles (PBs) were synthesized and characterized.
- ROS generation (hydroxyl radicals, hydroperoxyl radicals, singlet oxygen) was studied in an oxygen-independent pathway.
- PB's ROS scavenging capabilities and phototoxicity in normal tissues were assessed.
- Therapeutic efficacy was validated using an infected wound murine model.
Main Results:
- PBs generated hydroxyl radicals, hydroperoxyl radicals, and singlet oxygen independently of oxygen.
- PBs demonstrated the ability to scavenge ROS, maintaining redox homeostasis with negligible phototoxicity.
- Light irradiation allowed PBs to selectively regulate ROS generation and scavenging.
- PB-based PDT achieved significant therapeutic efficacy and accelerated healing in a murine wound model.
Conclusions:
- Prussian blue nanoparticles represent a novel class of photosensitizers for oxygen-independent PDT.
- PB-based PDT overcomes key limitations of traditional PDT, offering enhanced ROS diversity and selectivity.
- This discovery advances the understanding of PDT and paves the way for next-generation therapeutic strategies.
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