Biodegradable Persistent Luminescence Nanoparticles as Pyroptosis Inducer for High-Efficiency Tumor Immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunotherapy

Background:

• Pyroptosis is a potent antitumor immune mechanism, making pyroptosis inducers a promising strategy for cancer immunotherapy.
• Persistent luminescence nanoparticles (PLNPs) are valuable optical probes for tumor diagnosis and therapy, but their use as pyroptosis inducers is unexplored.

Purpose of the Study:

• To develop and characterize novel polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA) modified biodegradable CaS:Eu2+ (CSE@PP) persistent luminescence nanoparticles (PLNPs) as a pyroptosis inducer for tumor immunotherapy.
• To investigate the self-monitoring capabilities of these PLNPs based on their persistent luminescence (PersL) signal and their ability to induce pyroptosis via H2S and Ca2+ release.

Main Methods:

• Synthesis of PEG-PLGA modified biodegradable CaS:Eu2+ (CSE@PP) PLNPs.
• Evaluation of CSE@PP's pH-responsive degradation, persistent luminescence, and release of H2S and Ca2+ under acidic conditions mimicking the tumor microenvironment.
• Assessment of CSE@PP-induced intracellular oxidative stress, mitochondrial dysfunction, and pyroptosis (caspase-1/GSDM-D dependent) in tumor cells.
• Evaluation of the subsequent antitumor immune responses.

Main Results:

• The synthesized CSE@PP PLNPs exhibit biowindow persistent luminescence and pH-responsive degradation (degrading at pH < 6.5).
• CSE@PP gradually releases H2S and Ca2+ during degradation, with the fading PersL signal acting as a self-monitor for this release.
• The released H2S and Ca2+ synergistically induce intracellular oxidative stress, leading to pyroptosis and stimulating antitumor immune responses.

Conclusions:

• CSE@PP PLNPs serve as a novel, self-monitoring pyroptosis inducer for tumor immunotherapy.
• This development holds potential for advancing biomedical applications of PLNPs and inspiring new pyroptosis-based cancer immunotherapies.