Engineered cyanobacteria-based self-supplying photosensitizer nano-biosystem for photodynamic therapy

Cyanobacteria, due to its excellent oxygen production capability and desirable biocompatibility, have promising application prospects in oxygen-associated therapy, such as photodynamic therapy (PDT). Cyanobacteria-based PDT has emerged as an attractive microbial therapy. However, as the limited loading capacity of photosensitizer on cyanobacteria, it’s difficult to maintain a long and stable efficiency for cyanobacteria-based PDT. To break through this limitation, we designed and developed an engineered cyanobacteria (ECyano) using synthetic biology techniques. ECyano not only relieved the hypoxic tumour microenvironment, but also synthesized and accumulated 5-aminolevulinic acid (5-ALA) in tumour, generating reactive oxygen species (ROS) for killing tumours under laser irradiation. Then we attached manganese dioxide (MnO 2 ) nanoparticles to ECyano, thus creating a novel synergistic functional nano-biosystem, named as ECyano@MnO 2 . The combination of ECyano and MnO 2 was tuned to achieve PDT-immunotherapy. Upon the irradiation of 640 nm laser, ECyano@MnO 2 could firstly achieve self-supplying photosensitizer and oxygen, achieving the therapeutic effect. And then MnO 2 could act as an excellent adjuvant which could be degraded into Mn 2+ in tumour microenvironment and dendritic cells (DCs) were stimulated, eliciting potent anti-tumour immunity. The in vivo results showed partial tumour suppression of 79.34% treated with ECyano@MnO 2 . These results showed that engineered cyanobacteria-based nano-biosystem provided a promising strategy against tumour and may open the door to a promising microbial PDT.