Engineered Extracellular Vesicles to Enhance Antigen Presentation for Boosting Light-Driven Tumor Immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunotherapy

Background:

• Extracellular vesicles (EVs) are explored for cancer therapy but face challenges in antigen presentation by dendritic cells (DCs).
• Limited cross-presentation of tumor antigens by DCs hinders the efficacy of current EV-based immunotherapies.

Purpose of the Study:

• To develop engineered EVs (Te@EVs^HSP70) for combined photothermal therapy and immunotherapy.
• To enhance the tumor-targeting and immune-activating capabilities of EVs for cancer treatment.

Main Methods:

• Tumor cells were engineered to synthesize tellurium (Te) nanoparticles intracellularly.
• Near-infrared (NIR) irradiation was used to induce exocytosis of EVs overexpressing heat shock proteins 70 (HSP70) encapsulating Te nanoparticles (Te@EVs^HSP70).
• Photothermal performance, antigen capture, DC maturation, and antitumor efficacy of Te@EVs^HSP70 were evaluated in vitro and in vivo.

Main Results:

• Engineered Te@EVs^HSP70 demonstrated excellent photothermal conversion efficiency and enhanced tumor antigen capture.
• Te@EVs^HSP70 induced significant immunogenic cancer cell death and promoted DC maturation.
• The engineered EVs exhibited superior antitumor efficacy via photothermal effects and subsequent immune responses.

Conclusions:

• This study presents a straightforward method for fabricating multifunctional EVs for enhanced photothermal-triggered tumor immunotherapy.
• Engineered Te@EVs^HSP70 offer a promising strategy for improving cancer treatment by combining photothermal therapy with immunotherapy.