The controlled synthesis of degradable nanoparticles (NPs) made from a brush copolymer constituted of a 2-hydroxyethyl methacrylate (HEMA) backbone with PEG and PLA pendants both tunable in length and composition has been developed. Using ring-opening polymerization (ROP) of L,L–lactide, vinyl end-functionalized PLA macromonomers were produced and then copolymerized with HEMA–PEG macromonomers. Narrow dispersed PEGylated NPs with size down to 25 nm with different PEGylation degree and PEG chain lengths were obtained. Surfactant-free MSSEP in the absence of any solvent was implemented to produce NPs suitable for biomedical applications. The colloidal stability in isotonic solutions of these NPs was investigated and the corresponding critical coagulation concentration (CCC) of the NPs was determined.