Breast cancer is the most prevalent malignancy among women worldwide. Phototheranostics-an approach that uses light both to detect and treat cancerous lesions-has drawn growing attention due to its potential advantages, including light-triggered, non-invasive real-time diagnosis and simultaneous in situ therapy.
One promising strategy in light-based cancer treatment is photothermal therapy (PTT), which employs photothermal agents-ideally with tumor-targeting capability-to convert light irradiation into localized heat. However, challenges remain in the clinical translation of PTT, particularly the risks of overheating and damaging healthy tissue, as well as the potential failure to effectively ablate tumors.
In a study published in PNAS, a team led by ZHANG Pengfei from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences, in collaboration with Jong Seung Kim from Korea University, Jonathan L. Sessler from the University of Texas at Austin, and ZHOU Hui from the Nanjing University of Posts and Telecommunications, developed a dual-laser PTT (DLPTT) strategy for breast cancer therapy. This approach enhances tumor ablation while minimizing damage to surrounding healthy tissues by using near-infrared photothermal agents with aggregation-induced emission properties.
The dual-laser strategy operates in two stages. In the first stage, a short 808 nm laser irradiation (two minutes at approximately 50 °C) induces DNA damage and suppresses heat shock protein (HSP70) expression, thereby overcoming tumor resistance. The second stage is an extended 1,064 nm laser treatment (13 minutes at around 43 °C), which effectively ablates residual cancer cells with minimal inflammatory response.
This strategy employs second near-infrared (NIR-II) fluorescence imaging technology- a imaging modal with deeper penetration into tissues and less scattering producing dynamic image with higher signal to noise ratio-along with photoacoustic imaging approach. It permits highly precise targeting, as demonstrated in 4T1 breast cancer mouse models, where it significantly inhibited tumor growth without notable side effects. It also achieves clearer location of tumor in deeper tissue.
An in vivo biosafety experiment on mice showed that DLPTT effectively eradicated tumors while maintaining low toxicity, as evidenced by stable body weights and minimal production of inflammatory cytokines.
This study promotes the development of imaging-guided tumor phototherapy and extends research frontiers in aggregation-induced emission materials. Particularly, the future integration with immunotherapy will potentially provide a powerful means of addressing tumor metastasis and recurrence.
Schematic illustration of the DLPTT strategy designed to address the limitations of PTT. (Image by SIAT)
