Hydrogels and nanogels made from partially hydrolyzed poly(2-ethyl-2-oxazoline) (PEtOx) were prepared by two different processes. First, both hydrogels and nanogels were made in dilute media in the presence of 1,6-hexanediol di-glycidyl ether (1) as the cross-linker. Alternatively, the PEtOx precursor was engineered into nanogels by an inverse w/o emulsion process. In the latter case, in addition to cross-linker 1, a cleavable cross-linker homologue (2), namely 1,6-hydroxyethyl disulfide-bis-di-glycidyl ether, was used to produce cleavable nanogels. The pH-responsiveness of all cross-linked PEtOx derivatives was demonstrated in an acidic environment, owing to the protonation of residual ethylene imine groups and/or tertiary amines formed during the cross-linking reaction. Nanogels derived from cross-linker 2 could readily be cleaved under a reducing environment, due to the presence of disulfide linkages at the cross-linking points.