AIEgen-coupled upconversion nanoparticles eradicate solid tumors through dual-mode ROS activation.

Area of Science:

• Biomedical Engineering
• Immunology
• Nanotechnology

Background:

• Reactive oxygen species (ROS) play a crucial role in regulating antitumor immune responses.
• ROS can induce immunogenic cell death, enhance antigen presentation, and activate immune cells, but their controlled application in immunotherapy is challenging.

Purpose of the Study:

• To develop novel near-infrared (NIR)-driven immunostimulants by coupling upconversion nanoparticles with aggregation-induced emission luminogens (AIEgens).
• To harness the immunological effects of ROS for enhanced adaptive antitumor immune responses.

Main Methods:

• Synthesized AIEgen-upconversion nanoparticles for targeted ROS generation under NIR irradiation.
• Administered nanoparticles intratumorally and utilized dual-mode NIR irradiation (high-power for tumor, low-power for lymph nodes).
• Evaluated nanoparticle capacity for inducing immunogenic cell death, antigen capture, lymph node delivery, and T cell activation.

Main Results:

• Intratumoral injection and high-power NIR irradiation generated high-dose ROS, inducing immunogenic cell death and antigen release.
• Nanoparticles effectively captured and delivered released antigens to lymph nodes.
• Low-power NIR treatment of lymph nodes generated low-dose ROS, activating dendritic cells and robust T cell responses.
• The approach prevented both local tumor recurrence and distant tumor growth.

Conclusions:

• Developed a controllable platform using AIEgen-coupled upconversion nanoparticles for dual-mode NIR-driven ROS generation.
• This integrated approach effectively activates adaptive immune systems for enhanced tumor immunotherapy.
• The strategy shows promise for preventing local and distant tumor progression.