ROS Self-Supply Nanoplatform Based on Fenton Catalyst for Chemodynamic and Immunotherapy: Reprogramming Cold Tumor...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Immunosuppressive tumor microenvironments (TME) and "cold" tumors limit immunotherapy effectiveness.
• Minimal T cell infiltration in tumors hinders anti-cancer immune responses.
• Overcoming TME-mediated immunosuppression is crucial for improving cancer treatment outcomes.

Purpose of the Study:

• To develop a reactive oxygen species (ROS) self-supplying nanoplatform (HA-PGMC) for cancer therapy.
• To investigate the ability of HA-PGMC to convert "cold" tumors into "hot" tumors.
• To evaluate the potential of HA-PGMC in combination with immune checkpoint blockade therapy.

Main Methods:

• Fabrication of HA-PGMC using a metal-organic framework (MOF) loaded with glucose oxidase (GOx) and in situ grown copper peroxide (CuO2) nanodots.
• In vitro assessment of ROS generation, glutathione (GSH) depletion, lipid peroxidation, and mitochondrial dysfunction.
• Evaluation of immunogenic cell death (ICD) induction, including CRT exposure and HMGB1 release.

Main Results:

• HA-PGMC demonstrated significant ROS amplification and GSH depletion under tumor-specific conditions.
• In vitro studies showed potent antitumor effects with minimal toxicity to normal cells.
• HA-PGMC successfully induced ICD, promoting T cell infiltration and converting "cold" tumors to "hot" tumors.

Conclusions:

• The developed ROS-amplifying nanoplatform (HA-PGMC) shows promise for chemodynamic therapy (CDT).
• HA-PGMC effectively reprograms the tumor immune microenvironment, enhancing immunotherapy potential.
• This strategy offers a novel approach to overcome limitations in current cancer immunotherapy.