Exploring the Versatile Roles of Inorganic Polyphosphate Materials in Biological Systems

Polyphosphate (polyP), an ancient energy carrier and a compact inorganic polyanionic biopolymer, plays diverse roles in biological systems. Our research has explored its applications in protein phase transitions, microbial metabolism regulation, and nanotechnology, highlighting its potential in bioelectricity generation and nerve cell protection. We first investigated polyP's interaction with positively charged proteins, specifically +36GFP, showing that polyP induces liquid-liquid phase separation (LLPS) and forms protein coacervates through electrostatic interactions. This finding offers new insights into polyP's physiological functions.¹ In nanotechnology, we designed polyphosphate-based nanoparticles (PMNSs) that activated macrophages' innate immune response, suppressing tumor growth. PMNSs induced M1 macrophage polarization, secreting pro-inflammatory cytokines and activating the cGAS-STING pathway. In vivo, PMNSs inhibited tumor growth and activated antitumor responses.² Building on this, we synthesized STPE-PMNSs that mimic glutamine synthetase (GS) activity, converting glutamate to glutamine even without ATP. STPE-PMNSs alleviated neurotoxicity in SH-SY5Y cells, providing a new strategy for treating excitotoxic nerve cell damage.³ In summary, our research highlights polyphosphate's multifaceted roles, from enzyme mimicry and protein phase transitions to microbial metabolism regulation and bioelectricity enhancement. These findings underscore polyP's potential in nanotechnology, protein engineering, and microbial biotechnology, paving the way for innovative applications in science and industry.