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

  • ACS Appl Mater Interfaces. 2025 Oct 1;17(39):54453-54465. doi: 10.1021/acsami.5c10407.
Ting-Yu Cheng  1 ,  Li-Chan Chang  2 ,  Li-Xing Yang  1 ,  Sz-Syuan Wu  1 ,  Yu-Cheng Chin  1 ,  Ya-Jyun Chen  1 ,  Zi-Chun Chia  1 ,  Wen-Pin Su  2  3  4  5 ,  Chih-Chia Huang  1  5  6
Affiliations
  • 1. Department of Photonics, National Cheng Kung University, Tainan 701, Taiwan.
  • 2. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
  • 3. Departments of Oncology and Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
  • 4. Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
  • 5. Center of Applied Nanomedicine, National Cheng Kung University, Tainan 70101, Taiwan.
  • 6. Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
PMID: 40956059 DOI: 10.1021/acsami.5c10407
Abstract

Optical modulation of immune responses via nanomaterials has emerged as a promising approach in Cancer Immunotherapy, but challenges in achieving precise activation with minimal phototoxicity persist. In this study, we developed a galactose-functionalized Au-S (2ATP)/polyaniline (PANI)-based glycopolymer nanoparticle (Au/2ATP@PGlyco NP) to enable multivalent galactose-based biostimulation of M2-like macrophages and hot electron/hole-elicited Reactive Oxygen Species (ROS) generation for synergistic macrophage reprogramming. The 2ATP@PANI-based shell not only facilitated light-driven charge transfer to enhance 1O2 generation but also provided Raman-active properties that enabled single-cell visualization of phenotypic transitions toward the M1 phenotype through the NF-κB and STAT-1-mediated pro-inflammatory signaling. Such light-driven reprogrammed M1-like macrophages with Au/2ATP@PGlyco NP effectively induced Apoptosis in MB49 bladder Cancer cells through phagocytosis and the release of TNF-α and IL-12, resulting in a potent antitumor effect. This research highlights a new nanobiophotonics platform that holds potential for advancements in macrophage modulation within Cancer Immunotherapy.

Keywords
bioactive nanohybrids; immunotherapy; light-responsive nanoparticles; macrophage reprogramming; phototherapy.
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