Herein, we report the synthesis and characterization of monodisperse 'smart'
nanogels that exhibit a sharp volume phase transition at physiologically relevant temperatures and pH values. The
nanogels were prepared by precipitation copolymerization of
N-isopropylacrylamide (NIPAAm) and propylacrylic
acid (PAA). Briefly, the reaction was performed using a PAA feed of between 0 and 10 mol% in the presence of a crosslinker at 70 degrees C. The size of the
nanogel particles was determined as a function of pH and temperature using dynamic light scattering (DLS). At room temperature, the NIPAAm-PAA
nanogels were discrete, spherical structures with diameters ranging from 200 to 250 nm. The hydrodynamic diameter of the
nanogels decreased to ca. 100-150 nm when the
solution temperature was increased to 37 degrees C. At 37 degrees C, when the pKa was below that of the NIPAAm-PAA (ca. 6.0), the
gels collapsed and aggregated. However, at 37 degrees C and a physiological pH of 7.4, the
nanogels did not fully collapse due to the charge-charge repulsion derived from the ionized carboxyl groups of the PAA. Similar phase transition behavior was observed with the corresponding linear copolymers. Thus, such
nanogel particles could be useful for releasing drugs in regions of local
acidosis, including sites of
infection,
tumors,
ischemia, and intracellular endosomes.