A pH-insensitive fluorophore is fabricated to give pH-driven responses through its covalent incorporation within a nanostructure derived from pH-responsive polymers. Fluorophore shell-crosslinked nanoparticles (SCKs) demonstrate notable enhancement of photophysical properties in the physiological pH region. Fluorophore SCKs are designed to swell at higher pH values and shrink as the pH is lowered, producing high fluorescence versus low fluorescence outputs, respectively.