Chemotherapy-enabled/augmented cascade catalytic tumor-oxidative nanotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Catalytic cascade reactions are desirable for precise cancer therapy but challenging to engineer within the tumor microenvironment.
• Developing tumor microenvironment (TME)-responsive nanoreactors for synergistic cancer therapy remains a significant challenge.

Purpose of the Study:

• To engineer a tumor-specific nanoreactor capable of activating cascade reactions for oxidative stress-augmented chemotherapy.
• To investigate the synergistic therapeutic effects of combining chemotherapy with chemodynamic therapy (CDT) via a novel nanoreactor system.

Main Methods:

• Integration of a Pt(IV)-based prodrug with Cu(II)-based metal-organic frameworks (CuMOF) to create a CuMOF@Pt(IV) nanoreactor.
• Utilizing tumor cell internalization and glutathione (GSH) reduction to activate cascade reactions within the TME.
• Employing Cu+ ions for chemodynamic therapy (CDT) and elevated hydrogen peroxide (H2O2) levels to induce oxidative stress.

Main Results:

• The CuMOF@Pt(IV) nanoreactor effectively activated cascade reactions, leading to cisplatin release and elevated H2O2 levels.
• The nanoreactor depleted GSH, amplified tumor oxidative stress, and enhanced the therapeutic efficacy of Cu+-mediated CDT.
• Cooperative effects of chemotherapy and oxidative stress demonstrated significant antitumor efficacy in tumor-bearing mice with negligible adverse effects.

Conclusions:

• The developed cascade nanoreactor offers a promising strategy for precise cancer treatment by combining chemotherapy and oxidative stress.
• This approach provides a novel platform for developing complementary therapeutic modalities for enhanced cancer therapy.