Enzyme-Empowered "Two Birds with One Stone" Strategy for Amplifying Tumor Apoptosis and Metabolic Clearance

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Nanomedicine faces challenges in cancer treatment due to tumor defense mechanisms fueled by adenosine triphosphate (ATP).
• Tumor defenses include DNA repair, resistance to programmed cell death (apoptosis), and immune evasion, all relying on ATP.
• Overcoming these ATP-dependent defenses is crucial for improving nanomedicine efficacy.

Purpose of the Study:

• To develop a novel nanomedicine strategy to amplify enzyme-mediated tumor apoptosis and promote metabolic clearance.
• To create a dual-action approach targeting both tumor energy supply and nanomedicine clearance.
• To utilize glucose oxidase (GOx) and functionalized rhenium nanoclusters for enhanced cancer therapy.

Main Methods:

• A novel nanomedicine, GOx-functionalized rhenium nanoclusters-doped polypyrrole (Re@ReP-G), was synthesized.
• Re@ReP-G was designed to reduce ATP production and increase hydrogen peroxide (H2O2) via GOx enzymatic activity.
• Laser-induced hyperthermia was employed to further enhance tumor apoptosis.

Main Results:

• Re@ReP-G effectively reduced ATP production and increased H2O2 in the tumor microenvironment.
• This led to downregulation of protective proteins (HSP70, HSP90, Bcl-2) and upregulation of pro-apoptotic protein Bax.
• Cytochrome c release and severe tumor apoptosis were observed, alongside accelerated in vivo metabolic clearance of the nanomedicine.

Conclusions:

• The Re@ReP-G nanomedicine offers a "two birds with one stone" strategy for cancer therapy.
• It amplifies tumor apoptosis by disrupting energy metabolism and inducing cell death pathways.
• The strategy also ensures safe and efficient metabolic clearance of the nanomedicine in vivo.