Multicomponent polymeric micelles based on polyaspartamide as tunable fluorescent pH-window biosensors

Abstract

PHEA-PEG(5000)-C(16) is a polyaspartamide polymer with appended hydrophilic PEG(5000) functions and hydrophobic n-C(16) units forming biocompatible micelles with a CAC as low as 1.8 × 10(-7) M. The protonation and acidity constants of the polymer's amino and carboxylic groups have been determined by potentiometric titrations at five different concentrations higher than CAC, finding concentration-independent values. Viscosity and polarity of the micellar core have been investigated by means of fluorescent probes, finding local values comparable to those of pure toluene and to the core of sodium dodecyl sulphate micelles, independently on the protonation degree of the polymer. The fluorophore pyrene, the lipophilic N,N'-dimethyl-N"-dodecylamine and 2-dodecylpyridine self-assemble in the hydrophobic core of PHEA-PEG(5000)-C(16) micelles originating a micellar device that behaves as a rare "off-on-off" fluorescence sensor for pH windows, with no interference by the amino and carboxylic functions of the polymer. The "on" state of the sensor includes the physiological 6-8 pH interval, and can be finely shifted in both directions of the pH axis by comicellization of charged cosurfactants. Dialysis experiments demonstrate that the micellar device exibits an efficient retention ability of all molecular components, including cosurfactants, thus candidating for in vivo use.