Intracellular trafficking and excretion of PEGylated polymer-based nanoparticles in macrophages

• Κύριος συγγραφέας: Barbieri, Beatriz
• Γλώσσα: English
• Έκδοση: 2022
• Θέματα: Polymeric nanoparticles; Intracellular trafficking; Πολυμερικά νανοσωματίδια; Ενδοκυτταρική μεταφορά

Despite the increased interest in the application of nanoparticles (NPs) in medicine, nanotherapeutics still often suffer from a poor pharmacokinetic profile with a short half-life in blood. This is caused by the interactions between NPs and macrophages within the reticuloendothelial system. Macrophages sequester NPs from the bloodstream and hamper their therapeutic action. Aiming to formulate NPs with superior pharmacokinetic profile, Spago Nanomedical has developed proprietary PEGylated polymeric NPs with a diameter of 31 nm and a zeta potential of -1.33 mV. Although the pharmacokinetic profile of Spago’s NPs is considered very good, there is still some degree of macrophage uptake. Therefore, this study aimed to determine the uptake mechanism of NPs by RAW 264.7 murine macrophages, monitor NPs intracellular trafficking, and dissect the process of NP cellular excretion. Our results revealed that Spago’s proprietary NPs are endocytosed by RAW 264.7 murine macrophages mainly via scavenger receptor A in a clathrin-dependent manner. Once internalized, they are delivered to early endosomes, reaching the lysosomes at the end of its intracellular trafficking. After 24 h, about 30% of the NPs were eliminated by the macrophages. This work revealed the NP biofate in RAW murine macrophages. Comprehending how NPs are internalized and further processed by phagocytic cells contributes to the design of drug delivery systems with improved efficacy.