Highly Active Strontium Peroxide Nanoparticles Induce Alkalization/Oxidation to Potentiate Cancer Immuno-Metabolic...

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunology

Background:

• Hepatocellular carcinoma (HCC) presents a significant health challenge due to its immunosuppressive tumor microenvironment (TME) and acidosis.
• Current treatments struggle to overcome the TME's poor immunogenicity and metabolic dysregulation.
• Targeting the TME's metabolic and immune characteristics is crucial for effective HCC therapy.

Purpose of the Study:

• To develop an oxidation-alkalization strategy for immuno-metabolic regulation in HCC.
• To induce immunogenic cell death (ICD) and enhance anti-cancer immune responses.
• To investigate the role of lactic acid in modulating the immune response within the TME.

Main Methods:

• Synthesis of strontium peroxide nanoparticles (SrPN) via a mild liquid-phase approach.
• Utilizing SrPN to induce oxidative stress and alkalization in HCC cells.
• Evaluating SrPN efficacy in an orthotopic HCC model using ultrasound-guided percutaneous injection.

Main Results:

• SrPN effectively induced ICD in HCC cells, promoting dendritic cell maturation and M1 macrophage polarization.
• Alkalization reversed tumor-induced acidosis, while H2O2-mediated oxidative stress enhanced immune responses.
• Lactic acid amplified macrophage glycolytic levels, synergizing with SrPN to promote M1 polarization and anti-cancer immunity.
• SrPN demonstrated high tumor inhibition efficiency in vivo through combined cancer cell killing and TME immuno-metabolic regulation.

Conclusions:

• The developed oxidation-alkalization strategy using SrPN shows promise for potentiating HCC anti-cancer immunity.
• Metabolic regulation within the TME, leveraging intratumoral metabolites like lactic acid, is key to enhancing therapeutic outcomes.
• SrPN offers a biocompatible and effective approach for immuno-metabolic regulation in HCC treatment.