Revealing the Phagosomal pH Regulation and Inflammation of Macrophages after Endocytosing Polyurethane Nanoparticles by A Ratiometric pH Nanosensor

Abstract The effect of the intracellular pH of macrophages after taking up biodegradable polymer nanoparticles (NPs) on immunomodulating functions has not been explored so far. Previous studies have demonstrated that biodegradable polyurethane (PU) NPs exhibit immunosuppressive activity. Yet, the intracellular mechanism is not clearly understood. In this study, a uniquely designed pH nanosensor is employed for tracking the intracellular pH value of macrophages to reveal the intracellular journey of PU NPs and to clarify the intracellular pH effect on the corresponding inflammatory response. First, fluorescent mesoporous silica nanoparticles (FRMSNs) is used to detect the pH change in macrophages after endo/phagocytosis of PU NPs. Second, PU is coated on the external surface of FRMSNs to examine the intracellular trafficking process of PU in the macrophages. The results show that the majority of PU‐coated FRMSNs remain to stay at the cytosol‐early endosome/phagosome regions. The intracellular pH value and other supporting results show that the immune response of PU NPs may be correlated to their internalization journey. The retardation in the degradation process of the PU NPs may intervene with the lysosome activity and repress the immunostimulatory effect, which contributes to the low immune response of PU NPs.