NIR responsive nanosystem based on upconversion nanoparticle-engineered bacteria for immune/photodynamic combined therapy with bacteria self-clearing capability

Biological engineering bacteria hold great promise in tumor therapy due to their targeted delivery, tumor penetration, and tumor-specific activation capabilities. However, the use of live bacteria raises safety concerns, as they can potentially cause infections or adverse immune responses in patients. Additionally, most biological engineering bacteria are only responsive to blue light, which has limited penetration depth within biological tissues. To address these limitations, we have developed a nanoplatform that combines dual-emission upconversion nanoparticles (referred to as DDUCNPs), which can realize dual-wavelength emission under dual-wavelength excitation, with biological engineering bacteria for tumor treatment and the self-clearance of biological engineering bacteria after therapy in the near-infrared (NIR) window. This design allows us to utilize 980 nm light, which is converted to blue light by the DDUCNPs, to activate the bacteria and promote the controlled release of tumor necrosis factor-alpha (TNF-α) for precise tumor ablation. Subsequently, we employ 808 nm excitation to achieve light conversion into the red light, thereby activating photosensitizer molecules and generating singlet oxygen (ROS) for in vivo clearance of the bacteria involved in the treatment. Simultaneously, the generated ROS also undergoes photodynamic therapy (PDT) on the tumor to enhance the therapeutic effect. By combining these elements on a single platform, our system achieves the activation and self-clearance of biological engineering bacteria in the NIR window, effectively enabling tumor treatment. This approach overcomes the limitations of blue light penetration and addresses safety concerns associated with live bacteria, offering a promising strategy for precise and controlled tumor therapy.