CaCO₃-Assisted Preparation of pH-Responsive Immune-Modulating Nanoparticles for Augmented Chemo-Immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• The tumor microenvironment (TME) often hinders cancer therapy effectiveness.
• Modulating the TME is a promising strategy to improve therapeutic outcomes.
• Developing advanced drug delivery systems is crucial for overcoming treatment resistance.

Purpose of the Study:

• To create pH-responsive nanoparticles for co-delivery of doxorubicin (DOX) and an IDO1 inhibitor (aNLG919).
• To investigate the potential of these nanoparticles in enhancing chemo-immunotherapy by targeting the TME.
• To evaluate the anti-tumor efficacy and immune response modulation of the developed nanoparticles.

Main Methods:

• Utilized a CaCO3-assisted double emulsion method for nanoparticle preparation.
• Co-encapsulated doxorubicin (DOX) and alkylated NLG919 (aNLG919) into pH-responsive nanoparticles (DNCaNPs).
• Evaluated nanoparticle performance in vitro for cancer cell death and in vivo for tumor suppression in mouse models.

Main Results:

• DNCaNPs effectively induced immunogenic cell death (ICD) and inhibited immunosuppressive kynurenine production.
• Demonstrated efficient tumor accumulation, penetration, and neutralization of acidic TME.
• Significantly suppressed tumor growth in mouse models by increasing CD8+ T cells and decreasing regulatory T cells (Tregs).

Conclusions:

• Developed a strategy for pH-responsive nanoparticles for enhanced cancer chemo-immunotherapy.
• Successfully overcame the immunosuppressive TME to improve therapeutic responses.
• Presented a promising approach for combined chemotherapy and immunotherapy against cancer.