Local M1 Macrophage Reprogramming with Gluconic Acid-Coated Selenium Nanoparticles.

Area of Science:

• Nanotechnology
• Immunology
• Oncology

Background:

• Cytokine-based reprogramming of tumor-associated macrophages (TAMs) shows therapeutic promise but faces bioavailability challenges.
• Selenium (Se) and its selenoproteins are vital for regulating innate and adaptive immunity.

Purpose of the Study:

• To develop a novel method for enhancing macrophage function using selenium nanoparticles (GA-SeNPs).
• To evaluate the in vivo efficacy of GA-SeNPs in a melanoma mouse model for cancer therapy.

Main Methods:

• Gluconic acid-coated Se nanoparticles (GA-SeNPs) were synthesized.
• In vivo efficacy was assessed via intratumoral injection in a B16-F10 melanoma BALB/c mouse model.

Main Results:

• GA-SeNPs induced M2-to-M1 macrophage repolarization and inhibited tumor growth via reactive oxygen species (ROS) generation.
• Transcriptomic analysis revealed GA-SeNPs influence selenoprotein biosynthesis, oxidative phosphorylation, and inflammatory pathways.
• Treatment resulted in a >4-fold reduction in tumor weight and effectively repolarized TAMs to an M1 phenotype in vivo.

Conclusions:

• GA-SeNPs disrupt the immunosuppressive tumor microenvironment by repolarizing TAMs, inhibiting cancer growth.
• The dual localization of GA-SeNPs within TAMs and cancer cells highlights their therapeutic potential.
• This strategy offers a promising approach to advance TAM-based cancer therapies and improve clinical outcomes.