Black phosphorus nanosheets boost mitochondrial oxidative phosphorylation improving immunotherapy outcomes

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Intracellular phosphorus regulation impacts biosynthesis and cancer progression.
• Black phosphorus nanosheets (BPP) offer potential therapeutic applications.

Purpose of the Study:

• To investigate the metabolic fate and therapeutic effects of PEGylated black phosphorus nanosheets (BPP) in tumor cells.
• To evaluate BPP's impact on mitochondrial function, signaling pathways, and immune response in cancer.

Main Methods:

• Administration of exogenous PEGylated black phosphorus nanosheets (BPP) to tumor models.
• Metabolic analysis of BPP within tumor cells.
• Assessment of mitochondrial oxidative phosphorylation and signaling pathway modulation.
• Evaluation of immune cell populations (CD8+, CD4+ T cells) and cytokine levels.
• Analysis of PD-L1 protein expression and combination therapy with PD-1/PD-L1 inhibitors.

Main Results:

• BPP is metabolized into phosphate in tumor cells, enhancing mitochondrial oxidative phosphorylation.
• BPP treatment attenuated prosurvival gene expression and reduced PD-L1 protein in melanoma cells, impairing cancer progression.
• BPP promoted immune activation, increasing proinflammatory cytokines, CD8+ T cells, and effector memory CD8+ T cells, while decreasing regulatory CD4+ T cells.
• Combination therapy with PD-1/PD-L1 inhibitors amplified BPP's immunopotentiation effect.

Conclusions:

• PEGylated black phosphorus nanosheets (BPP) act as a dual-function agent, exhibiting chemotherapeutic and immunopotentiating properties.
• BPP's metabolism to phosphate and subsequent modulation of cellular processes offer a novel therapeutic strategy.
• BPP holds promise for enhancing anti-tumor immunity and improving cancer treatment outcomes.