Bioactive Light-Responsive Au Nanohybrids for Reactive Oxygen Species-Driven Macrophage Reprogramming

Area of Science:

• Nanomedicine
• Cancer Immunotherapy
• Biophotonics

Background:

• Optical modulation of immune responses via nanomaterials is promising for cancer immunotherapy.
• Challenges remain in precise activation and minimizing phototoxicity.

Purpose of the Study:

• To develop a galactose-functionalized nanoparticle for biostimulation and reactive oxygen species (ROS) generation.
• To achieve synergistic macrophage reprogramming for enhanced cancer treatment.

Main Methods:

• Developed galactose-functionalized Au-S (2ATP)/polyaniline (PANI)-based glycopolymer nanoparticles (Au/2ATP@PGlyco NP).
• Utilized light-driven charge transfer for ROS generation and Raman-active properties for single-cell visualization.
• Investigated NF-κB and STAT-1 signaling pathways for macrophage phenotype transition.

Main Results:

• Au/2ATP@PGlyco NP enabled multivalent galactose biostimulation and ROS generation.
• Successfully reprogrammed M2-like macrophages to M1-like phenotype.
• Light-driven M1-like macrophages induced apoptosis in MB49 bladder cancer cells via phagocytosis and cytokine release (TNF-α, IL-12).
• Demonstrated potent antitumor effects.

Conclusions:

• The developed nanobiophotonics platform offers a novel approach for macrophage modulation in cancer immunotherapy.
• Au/2ATP@PGlyco NP shows potential for precise cancer treatment with reduced phototoxicity.
• This strategy synergistically combines optical stimulation and immune cell reprogramming for effective antitumor responses.