文献类型：期刊文献

英文题名：Visualizing and Modulating Lysosomal pH in Macrophages via Internalization and Degradation of Polyglycolic Acid Particles

作者：Xie, Bowen[1,2]; Lan, Tian[1]; Zhang, Jiapeng[1,3]; Cen, Lian[3]; Xi, Zhenhao[3]; Yang, Ying[1]

机构：[1] Guy Hilton Research Centre, School of Life Science, Keele University, Stoke-on-Trent, ST4 7QB, United Kingdom; [2] Institute of Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; [3] Shanghai Key Laboratory of Multiphase Materials Chemical Engineering, Department of Product Engineering, School of Chemical Engineering, East China University of Science and Technology, Shanghai, 200237, China

年份：2025

外文期刊名：SSRN

收录：EI(收录号：20250458217)

语种：英文

外文关键词：Acidification - Biodegradation - Biomaterials - Degradation - Immune system - Induced polarization logging - Particles (particulate matter) - pH effects - Physiology - Polarization

摘要：Macrophages, key players in the immune response, undergo polarization into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes upon receiving external stimuli. Alterations in lysosomal pH values within macrophages regulate the polarization process. The internalization of degradable polyester particles may interfere with the lysosomal pH of macrophages. This study investigated how internalized poly(glycolic acid) (PGA) particles with different degradation rates induced lysosomal acidification in murine macrophages (RAW 264.7) and modulated their phenotypic polarization. Lysosomal pH changes and particle internalization were monitored using a pH-sensitive fluorescent dye and PGA particles tagged with Fluorescein isothiocyanate (FITC). Real-time imaging and quantitative measurements of pH alterations following PGA internalization were conducted. The findings revealed that culturing/internalizing 20 PGA particles per cell with a fast acidification rate (from pristine porous foam) induced pro-inflammatory responses in M0 and M1 macrophages, characterized by increased M1 cytokine secretion and biomarker expression. In contrast, culturing/internalizing 20 PGA particles per cell with slower acidification rates (from partially degraded foam) promoted the polarization of M0 macrophages to an M2 macrophages, as evidenced by increased M2 marker expression and cytokine secretion. V-ATPase, a key regulator of lysosomal pH, was inhibited in M1 macrophages by internalization of PGA particles, whereas it was activated in M2 macrophages, thereby further supporting the anti-inflammatory effects. These results confirm that the acidification of PGA particles and their acidification rate can modulate macrophage polarization intracellularly and further affect inflammatory responses. This study highlights the potential of degradable biomaterials in regulating immune responses and provides a foundation for designing biomaterials with targeted immunomodulatory effects. ? 2025, The Authors. All rights reserved.