Acidic and hypoxic tumor microenvironment regulation by CaO₂-loaded polydopamine nanoparticles

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Tumor microenvironment (TME) characterized by hypoxia and lactic acid promotes cancer progression.
• Existing therapies face challenges in effectively targeting these TME aspects.

Purpose of the Study:

• To develop a nanostructure capable of simultaneously addressing tumor hypoxia and lactic acid accumulation.
• To investigate the therapeutic potential of this nanostructure in repressing tumor progression.

Main Methods:

• Calcium peroxide (CaO2)-loaded mesoporous polydopamine nanoparticles modified with sodium hyaluronate (CaO2@mPDA-SH) were synthesized.
• The nanostructure's ability to consume lactic acid and generate oxygen in acidic conditions was evaluated.
• The impact on hypoxia-inducible factor-1α (HIF-1α) and downstream glycolysis enzymes (GLUT1, LDHA) was assessed.

Main Results:

• CaO2@mPDA-SH nanoparticles effectively accumulated in tumor sites.
• The nanostructure normalized the acidic and hypoxic TME by consuming lactic acid and producing oxygen.
• Hypoxia relief led to downregulation of HIF-1α, GLUT1, and LDHA, reducing lactate production.
• The nanostructure alone demonstrated significant repression of tumor progression, metastasis, and angiogenesis, while promoting immune activation.

Conclusions:

• CaO2@mPDA-SH nanostructures offer a dual-action therapeutic strategy for TME normalization.
• This approach shows promise for inhibiting tumor progression, metastasis, and angiogenesis.
• The nanostructure presents a potential standalone therapy for various cancers.