Visible Light Modulates Macrophage Phenotype and Photoresponsive Carbon Monoxide Delivery

This is the authors' abstract. We don't add key points for this paper.

Photoresponsive drug delivery systems are often described as bioorthogonal. However, certain wavelengths and intensities of visible light are known to modulate cellular phenotypes. This apparent discrepancy highlights a gap in knowledge with direct implications for the design of photoresponsive drug delivery systems. In this report, we investigated the response of primary macrophages to visible light (405–630 nm) due to their broad tissue distribution, phenotypic plasticity, and central role in orchestrating immune responses across diverse pathologies. We found distinct wavelength-dependent changes in cytochrome c oxidase activity, metabolic function, cytokine secretion, and biomarker expression at clinically relevant intensities of light. Further investigation of red light (630 nm) demonstrated complex dose-dependent metabolic and phenotypic responses. To illustrate the clinical implications of these findings, we employed 470 nm-triggerable carbon monoxide-releasing micelles to deconvolute the individual and combined effects of light exposure and therapeutic payloads. Our findings suggest that macrophages respond in a wavelength and intensity-dependent manner, and incorporating photoresponsive carbon monoxide-releasing systems elicits distinct immunomodulatory responses compared to irradiation alone. This work establishes a basic design framework for leveraging light parameters such as wavelength and intensity to achieve desirable immunomodulatory responses with photoresponsive drug delivery systems for specific disease applications.