Living Biotherapeutics Using Nanoparticles-Armed Cyanobacteria for Boosting Photodynamic-Immunotherapy of Cancer.

The interdisciplinary development of synthetic biology and material sciences propels medicine into a new era. For cancer therapy, living biotherapeutics integrating functional living bacteria with nanomedicine are particularly interesting. The current study developed a living biotherapeutic platform integrating oxygen-self-supplying cyanobacteria with multifunctional prodrug nanoparticles to boost photodynamic immunotherapy. Generally, tetracarboxyl porphyrin is associated with cisplatin via a covalent self-assembly strategy into uniform prodrug-skeletal nanoparticles (ZnNCs). This helped encapsulate the antitumor drug dicumarol derivative (DicTBS). Later, these developed DicTBS-ZnNC nanoparticles helped arm the surface of cyanobacteria using electrostatic adsorption to yield living nanotherapeutics (Cyano@DicTBS-ZnNCs). Cyano@DicTBS-ZnNCs achieved a self-supply of nanoparticles and oxygen under 660 nm laser irradiation, producing PDT therapeutic effects. Furthermore, combining cisplatin and dicoumarol achieved synergistic anticancer effects. This approach also induced immunogenic cell death (ICD) and regulated the tumor microenvironment (TME). This promoted an immune-supportive environment to improve antitumor immune responses.