Thermo-responsive molecularly imprinted nanogels for specific recognition and controlled release of proteins

Intelligent nanogels which respond to environmental stimuli with on/off characteristics hold great promise in a number of biomedical applications including drug/gene delivery, diagnostics and therapeutics. Here, we report the synthesis and characterization of a novel type of thermo-responsive nanogel built using the molecular imprinting technique for specific recognition and controlled release of proteins. Using lysozyme as the protein template and N-isopropylacrylamide as the major monomer, protein-imprinted spherical nanogel particles were readily prepared via aqueous precipitation polymerization with the aid of a surfactant, sodium dodecyl sulfate (SDS). Simply by adjusting the SDS amount during polymerization, the size of nanogels could be finely controlled, ranging from a few hundred down to a few dozen nanometers. Compared to non-imprinted counterparts, the lysozyme-imprinted nanogels possessed higher rebinding capacity, more rapid rebinding kinetics, and much higher specificity toward lysozyme. Importantly, both the rebinding and release characteristics of lysozyme-imprinted nanogels showed dramatic temperature-dependence, with clear on–off transition around 33 °C, i.e., the volume phase transition temperature of the thermo-responsive polymer poly(N-isopropylacrylamide). Therefore, we have developed a facile yet versatile approach to fabricate molecularly imprinted nanogels of well controlled sizes and thermo-responsive binding/release properties toward specific biomolecules, which may facilitate a broad spectrum of applications ranging from bioseparation and biosensing to drug delivery and therapeutics.