A pH‐Responsive Nanoparticle Library with Precise pH Tunability by Co‐Polymerization with Non‐Ionizable Monomers

Abstract Precise monitoring of the subtle pH fluctuation during biological events remains a big challenge. Previously, we reported an ultra‐pH‐sensitive (UPS) nanoprobe library with a sharp pH response using co‐polymerization of two tertiary amine‐containing monomers with distinct p K a . Currently, we have generalized the UPS nanoparticle library with tunable pH transitions (pH t ) by copolymerization of a tertiary amine‐containing monomer with a series of non‐ionizable monomers. The pH t of nanoparticles is fine‐tuned by the non‐ionizable monomers with different hydrophobicity. Each non‐ionizable monomer presents a constant contribution to pH tunability regardless of tertiary amine‐containing monomers. Based on this strategy, we produced two libraries of nanoprobes with continuous pH t covering the entire physiological pH range (5.0–7.4) for fluorescent imaging of endosome maturation and cancers. This generalized strategy provides a powerful toolkit for biological studies and cancer theranostics.