Hydrogen bonding is widely present and plays a significant role in material science and supramolecular chemistry. This work reports a straightforward strategy for the preparation of polymeric nanoparticles from neutral poly(2-oxazoline)s (POx) and tannic acid (TA) driven by their intermolecular hydrogen bonding. Dynamic light scattering (DLS) and scanning electron microscope (SEM) measurements showed that POx bearing different substituents, that is, methyl, ethyl and n-propyl in the 2-position all could assemble with TA into stable nanoparticles in water or ethanol. The diameter of the assembled nanoparticles could be manipulated by varying parameters such as molecular weight of POx, concentration and ratio of POx, and TA. Interestingly, POx/TA nanoparticles exhibited upper critical solution temperature (UCST)-type thermoresponsive properties in ethanol or water depending on the molecular weight and substituent in the 2-position of POx. Increasing or decreasing the temperature at the transition point resulted in the reversible transformation between assembled nanoparticles and disassembled poly(2-n-propyl-2-oxazoline) (PnPrOx) and TA. In view of the tailored size of the stable nanoparticles and the biocompatibilities of POx and TA, the prepared thermoresponsive nanoparticles are promising candidates as carriers for medicine toward related biomedical applications. (c) 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1520-1527