Studies of the radiation-induced synthesis of poly(vinylpyrrolidone) (PVP) nanogels, intended to provide a basis for obtaining intra-molecular cross-linked products, which are more useful in drug delivery, show that a sharp change in the controlling mechanism from inter-molecular to intra-molecular cross-linking occurs above a threshold temperature around 50 degrees C-55 degrees C, even though the rate of inter-molecular cross-linking is enhanced as the temperature is raised. When aqueous solutions of PVP are irradiated, the activation energy of the decay of the PVP. radical is observed to rise sharply above this threshold temperature. This can be attributed to the collapse of the polymer chains, which occurs at temperatures above approximately 55 degrees C and leads to a reduction of the R(h) of the irradiated polymer molecules at 77 degrees C to (44 +/- 3) % of that of PVP molecules that were not irradiated at 20 degrees C, as shown by the results of AFFFF measurements. The abrupt transition to a mechanism controlled by intra-molecular cross-linking is due to the thermal collapse of the polymer structure. This accounts for the observation that activation energy is higher within the temperature range above 55 degrees C. Higher pulse repetition rates during electron irradiation also promote intra-molecular cross-linking. (C) 2011 Elsevier Ltd. All rights reserved.