Lanthanum Carbonate Nanosheets Based Colloidal Hydrogel for Modulating Innate & Adaptive Tumor Immunotherapy by...

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunotherapy

Background:

• Cellular pyroptosis is a promising cancer immunotherapy strategy.
• Gene methylation, particularly of gasdermin E (GSDME), hinders pyroptosis in cancers like triple-negative breast cancer (TNBC).

Purpose of the Study:

• To develop a novel colloidal hydrogel (GDLC hydrogel) for targeted pyroptosis induction in TNBC.
• To investigate the synergistic effects of decitabine (DAC) and lanthanum ions (La3+) in reversing GSDME gene silencing and activating pyroptosis.

Main Methods:

• Formulation of a GDLC hydrogel loaded with decitabine (DAC) and crosslinked with lanthanum carbonate nanosheets (LCNSs) and gelatin nanoparticles (Gela NPs).
• In vitro and in vivo evaluation of the hydrogel's ability to induce pyroptosis in 4T1 TNBC cells.
• Assessment of epigenetic modification reversal, caspase-3 activation, and anti-tumor immune responses.

Main Results:

• The GDLC hydrogel effectively induced pyroptosis in 4T1 TNBC cells by reversing GSDME gene silencing and activating caspase-3.
• DAC and La3+ demonstrated synergistic effects in the tumor microenvironment (TME).
• Combination therapy with the GDLC hydrogel and immune checkpoint inhibitors neutralized immunosuppression, triggered anti-tumor immunity, and established immune memory, significantly reducing tumor recurrence and metastasis.

Conclusions:

• The developed GDLC hydrogel platform offers an innovative approach for TNBC immunotherapy.
• This strategy shows potential for overcoming GSDME silencing and enhancing anti-tumor immune responses.
• The hydrogel system holds promise for improving therapeutic outcomes in triple-negative breast cancer.