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

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 pK_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.