Recently, electro-Fenton (EF) process has been shown as a promising, facile, effective, low cost and environmentally-friendly alternative for synthesizing polymer nanogels suitable as biocompatible nanocarriers for emerging biomedical applications. Here, the electrochemically-assisted modification of poly(vinylpyrrolidone) (PVP) by EF process was studied to assess the role of key operation parameters for a precise modulation of polymer crosslinking and its functionalization with [sbnd]COOH and succinimide groups. The dimensions of the nanogels, in terms of hydrodynamic radius (Rh) and weight-average molecular weight (Mw), can be tuned up by controlling the electrolysis time, current density (j) and PVP and Fe2+concentrations, as demonstrated via dynamic and static light scattering and gel permeation chromatography analysis. Using PVP at 0.25 wt.%, Fe2+at 0.5-1.0 mmol dmâ\u88\u923and low j, short treatment times induced intramolecular crosslinking with chain scission, allowing size reduction of PVP particles from 24 to 9â\u80\u9310 nm. Longer reaction times and higher PVP and Fe2+contents favored intermolecular crosslinking ending in Mwvalues higher than the initial 3.95 Ã\u97 105 g molâ\u88\u921. An excessive [rad]OH dose from a too high circulated charge (Q), i.e., too prolonged electrolysis time even at low j or too high j even for short time, promoted intramolecular crosslinking (Rh â\u88¼Â 10â\u80\u9312 nm) along with a very significant chain scission probably owing to the loss of mobility of the three-dimensional nanogel network. In conclusion, EF allowed transforming the architecture of linear, inert PVP chains into a functionalized nanogel with [sbnd]COOH and succinimide groups that have great potential for further conjugation