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.