A long-term self-driven metronomic photodynamic system for cancer therapy

Weili Wang, Binglin Ye, Yao Liu, Zhi Li, Qianying Huang, Jialin Zhou, Min Hu, Jun Jiang, Weilin Wang (), Zhengwei Mao () and Yuan Ding ()
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Weili Wang: Zhejiang University School of Medicine
Binglin Ye: Zhejiang University School of Medicine
Yao Liu: Zhejiang University School of Medicine
Zhi Li: Soochow University
Qianying Huang: Zhejiang University School of Medicine
Jialin Zhou: Zhejiang University School of Medicine
Min Hu: Zhejiang University School of Medicine
Jun Jiang: Zhejiang University School of Medicine
Weilin Wang: Zhejiang University School of Medicine
Zhengwei Mao: Zhejiang University School of Medicine
Yuan Ding: Zhejiang University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Metronomic photodynamic therapy is a long-term, low-dose treatment strategy that employs optical devices with continuous photosensitizer administration and requires stable device attachment with a consistent power source. These factors significantly limit patient mobility. Currently, no metronomic photodynamic therapy modality can operate independent of external devices, underscoring the critical need for in vivo light sources that function without external energy inputs. In this study, we integrate self-luminous bacteria with a photosensitizer in alginate microcapsules to create a self-driven metronomic photodynamic therapy that can be securely implanted within a tumour, thereby enabling continuous light emission without requiring an external energy source or ongoing replenishment of photosensitive reactants. By harnessing nutrients from the tumour microenvironment, this system sustains the generation of reactive oxygen species. A single injection effectively eliminates larger tumours (>300 mm3) in an opaque melanoma mouse model and transplanted hepatocarcinoma rabbit model. Self-driven metronomic photodynamic therapy demonstrates advantages over traditional photodynamic therapy, indicating its potential as a versatile therapeutic approach for cancer treatment with deeply situated lesions.

Date: 2025
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DOI: 10.1038/s41467-025-63868-3

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