Tumor Microenvironment-responsive Nanocatalyst for Targeted Chemodynamic Cancer Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Materials Science

Background:

• Challenges in cancer therapy include insufficient hydrogen peroxide (H2O2) levels, rapid Fe3+ precipitation, and slow Fenton reaction kinetics.
• Developing efficient catalysts for tumor microenvironment (TME) activation is crucial for enhanced therapeutic outcomes.

Purpose of the Study:

• To synthesize tumor-activated, self-accelerating catalytic nanocatalysts for enhanced cancer therapy.
• To improve tumor targeting, H2O2 responsiveness, and Fenton reaction efficiency.

Main Methods:

• Synthesized poly (lactic-co-glycolic acid) (PLGA)-encapsulated Ca-Fe peroxide clusters and polyarginine (R) nanocatalysts.
• Camouflaged nanocatalysts with cancer cell membranes (CCM) for enhanced tumor targeting.
• Utilized polyarginine to tailor PLGA responsiveness to low H2O2 levels and facilitate nitric oxide (NO) release.

Main Results:

• Achieved a 6.5-fold increase in homotypic tumor targeting and deep spheroid penetration (>120 µm).
• Demonstrated sustained Fenton reaction with amplified hydroxyl radical (•OH) generation due to H2O2-triggered PLGA degradation and NO release.
• Exhibited dose-dependent cytotoxicity, with polyarginine significantly reducing the IC50 value (from 216.9 to 43.38 µg mL⁻¹).
• Induced preferential necrosis, inhibiting tumor cell proliferation by 76.3% ± 8.4% over 7 days.

Conclusions:

• The TME-responsive, self-accelerating CDT platform enhances therapeutic efficacy through improved tumor targeting and amplified radical generation.
• CCM-PLGA-CaFe-R NPs offer a promising strategy for effective cancer treatment by overcoming limitations of traditional Fenton-based therapies.