Methylmethacrylate copolymer nanoparticles with diVerent hydrophilic chains were prepared by the free radical polymerization of methylmethacrylate with N-isopropylacrylamide (NIPAAm), N-methacrylic acid (MAA), N-trimethylaminoethylmethacrylate chloride (TMAEMC) or N-dimethylaminoethylmethacrylate hydrochloride (DMAEMC). These particles were characterized by particle size and zeta potential. The polymerization conditions were shown to inXuence the particle size and surface charge. Particle sizes of MMA-NIPAAm nanoparticles after 3h of reaction reached constant level at 180 nm. An increasing amount of total monomer (0.5-5%) would result in the nanoparticles of particle size of 115-204nm for 30% NIPAAm of the total monomer. In the same range of 5-40% NIPAAm of the total monomer, the particle size decreased from 280 to 170nm. The concentration of the initiator APS up to a concentration of 0.2% for MMA-TMAEMC and 0.1% for MMA-NIPAAm showed no eVect on the particle size of the Wnal nanoparticle suspensions, while higher concentration would lead to aggregation in the polymerization process. MMA-NIPAAm nanoparticles were pH-dependent in zeta potential at pH 1-12 values reducing from 12.2mV to ?16.8mV, respectively. Nanoparticles were incubated with pepsin and trypsin at 37℃ for 20min and their enzyme inhibition was determined. The activity of pepsin decreased to 27% in the presence of MMA-NIPAAm nanoparticles, and MMA-MAA nanoparticles reduced the activity of trypsin to 39%, respectively.