Self-passivated bilayer black phosphorus QDs based multifunctional nanoparticles for tumor immune reprogramming.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• The immunosuppressive tumor microenvironment hinders effective immunotherapy.
• Developing biosafe agents to enhance immunotherapy responses is crucial but challenging.
• Multimodal therapeutic strategies are needed to overcome tumor resistance.

Purpose of the Study:

• To construct and evaluate a novel nanoplatform (BD3PP) for synergistic multimodal therapy and imaging.
• To investigate the potential of BD3PP in overcoming the immunosuppressive tumor microenvironment for enhanced immunotherapy.
• To ensure the biosafety and efficacy of the developed nanoplatform for anti-tumor applications.

Main Methods:

• Construction of BD3PP: PLGA nanoparticles encapsulating black phosphorus quantum dots (BPQDs), thioredoxin reductase inhibitor 3c, and fluorescent dye Dir, conjugated with a PDL1 antagonist.
• Mechanism and efficiency evaluation using density functional theory (DFT) calculations, molecular docking, and in vitro/in vivo experiments.
• Assessment of photothermal therapy, photodynamic therapy, targeted therapy, and real-time imaging capabilities.

Main Results:

• Self-passivated bilayer BPQDs demonstrated superior photothermal and photodynamic therapy capabilities.
• 3c selectively inhibited thioredoxin reductase, inducing reactive oxygen species (ROS) production.
• BD3PP synergistically induced immunogenic cell death (ICD), promoted M1 macrophage polarization, and remodeled the tumor microenvironment, with Dir enabling real-time imaging.

Conclusions:

• BD3PP is an efficient and biosafe nanoplatform for integrated photothermal, photodynamic, and targeted therapies.
• The nanoplatform exhibits prolonged blood circulation and enhanced multimodal imaging capabilities.
• BD3PP shows significant promise for preclinical and clinical anti-tumor applications.