The application of piceatannol, a natural phenol compound with chemopreventive property against chemically induced cancer, has been limited because of its hydrophobicity and low bioavailability. This limitation can be overcome by associating it with a delivering carrier. Thermoresponsive poly (N-isopropylacrylamide) is attractive for drug delivery applications due to its expanded coil to collapsed globule transition close to physiological temperature. In this work, poly (N-isopropylacrylamide) was prepared via reversible addition-fragmentation chain transfer polymerization and its molecular weight and hydrodynamic diameter were measured by gel permeation chromatographer and dynamic light scattering, respectively. Fluorescence spectroscopy and isothermal titration calorimetry studies indicated that there are two types of sites on poly (N-isopropylacrylamide) molecules for the binding of piceatannol, i.e., hydrophilic and hydrophobic binding sites. The number of binding sites and the binding strength show pH-and temperature-responsiveness. In addition, the free concentration of piceatannol calculated from thermodynamic data implies that it has the maximum free concentration at 25 degrees C and pH 6.2, which indicates that properly acidic medium and lower temperature are favorable to its release. (C) 2016 Elsevier Ltd. All rights reserved.