Multifunctional MnO₂ nanoparticles for tumor microenvironment modulation and cancer therapy

Area of Science:

• Nanomedicine
• Oncologic Disease
• Therapeutic Approaches

Background:

• The tumor microenvironment (TME) exhibits low pH, high glutathione (GSH), excess hydrogen peroxide (H2O2), and hypoxia, promoting tumor progression and drug resistance.
• TME-responsive smart nanosystems offer potential for improved cancer treatment efficacy.
• Manganese dioxide (MnO2)-based nanosystems are recognized for their tunable properties, pH-responsive degradation, and catalytic activities, making them suitable for TME modulation.

Purpose of the Study:

• To review strategies employing MnO2 and its nanocomposites for modulating the TME.
• To highlight the application of MnO2-based nanoplatforms in various cancer therapies.
• To discuss challenges and future perspectives of MnO2-based nanosystems in oncology.

Main Methods:

• Summarizing MnO2-based strategies for TME modulation including hypoxia relief, GSH depletion, glucose consumption, and immunosuppression moderation.
• Highlighting representative MnO2 nanoplatform designs for tumor therapy.
• Reviewing therapeutic applications such as photodynamic, radiotherapy, sonodynamic, chemodynamic, starvation, and immunotherapy.

Main Results:

• MnO2-based nanosystems can effectively modulate key TME factors like hypoxia and GSH levels.
• These modulated TME conditions enhance the efficacy of diverse cancer treatment modalities.
• Representative MnO2 nanoplatforms demonstrate significant potential in preclinical tumor models.

Conclusions:

• MnO2-based nanosystems represent a versatile platform for TME-responsive cancer theranostics.
• Modulating the TME with MnO2 holds significant promise for advancing multiple cancer treatment strategies.
• Further research is needed to address challenges and fully realize the clinical potential of these nanomedicines.