A new strategy for the preparation of nanogels from commercially available monomers of bisepoxide and aliphatic polyetheramine has been developed. The nanogels are generated in a one-pot process through aggregation polymerization of an in situ formed thermal sensitive intermediate polymer in an additive-free and catalyst-free aqueous environment. Such a facile process allows easy size tuning of the gel particles from the nanometer to the micron scale, simply by adjusting the reactant concentration. The obtained nanogels demonstrated responsiveness to multiple biologically relevant stimuli, including temperature, pH, and oxidation. Nile red was encapsulated in the nanogels as a model hydrophobic drug. In vitro drug release studies showed stimuli-triggered release from the nanogels, suggesting the potential for controlled drug delivery.