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

Area of Science:

• Biomedical Engineering
• Materials Science
• Nanotechnology

Background:

• Accurate monitoring of pH fluctuations in biological systems is crucial but challenging.
• Previous ultra-pH-sensitive (UPS) nanoprobes utilized co-polymerization of tertiary amine monomers with distinct pK_a values.
• Generalizing UPS nanoprobes requires a strategy for tunable pH transitions (pH_t).

Purpose of the Study:

• To generalize the UPS nanoprobe library for tunable pH transitions.
• To fine-tune nanoparticle pH_t using non-ionizable monomers with varying hydrophobicity.
• To create nanoprobes for fluorescent imaging of endosome maturation and cancer theranostics.

Main Methods:

• Copolymerization of a tertiary amine-containing monomer with a series of non-ionizable monomers.
• Tuning nanoparticle pH_t by selecting non-ionizable monomers with different hydrophobicity.
• Developing two nanoprobe libraries with continuous pH_t across the physiological pH range (5.0–7.4).

Main Results:

• A generalized strategy for creating UPS nanoparticles with tunable pH_t was established.
• Each non-ionizable monomer contributed consistently to pH tunability.
• Two distinct nanoprobe libraries were successfully produced, covering the physiological pH range.

Conclusions:

• The generalized strategy enables fine-tuning of nanoparticle pH_t through non-ionizable monomer selection.
• This approach provides a versatile toolkit for biological studies, including endosome maturation imaging.
• The developed nanoprobes are valuable for cancer theranostics and precise pH monitoring.