A Novel Approach for the Synthesis of Responsive Core–Shell Nanogels with a Poly(N-Isopropylacrylamide) Core and a Controlled Polyamine Shell

Microgel particles can play a key role, e.g., in drug delivery systems, tissue engineering, advanced (bio)sensors or (bio)catalysis. Amine-functionalized microgels are particularly interesting in many applications since they can provide pH responsiveness, chemical functionalities for, e.g., bioconjugation, unique binding characteristics for pollutants and interactions with cell surfaces. Since the incorporation of amine functionalities in controlled amounts with predefined architectures is still a challenge, here, we present a novel method for the synthesis of responsive core-shell nanogels (<i>d_h</i> < 100 nm) with a poly(<i>N</i>-isopropylacrylamide) (pNIPAm) core and a polyamine shell. To achieve this goal, a surface-functionalized pNIPAm nanogel was first prepared in a semi-batch precipitation polymerization reaction. Surface functionalization was achieved by adding acrylic acid to the reaction mixture in the final stage of the precipitation polymerization. Under these conditions, the carboxyl functionalities were confined to the outer shell of the nanogel particles, preserving the core's temperature-responsive behavior and providing reactive functionalities on the nanogel surface. The polyamine shell was prepared by the chemical coupling of polyethyleneimine to the nanogel's carboxyl functionalities using a water-soluble carbodiimide (EDC) to facilitate the coupling reaction. The efficiency of the coupling was assessed by varying the EDC concentration and reaction temperature. The molecular weight of PEI was also varied in a wide range (<i>M_w</i> = 0.6 to 750 kDa), and we found that it had a profound effect on how many polyamine repeat units could be immobilized in the nanogel shell. The swelling and the electrophoretic mobility of the prepared core-shell nanogels were also studied as a function of pH and temperature, demonstrating the successful formation of the polyamine shell on the nanogel core and its effect on the nanogel characteristics. This study provides a general framework for the controlled synthesis of core-shell nanogels with tunable surface properties, which can be applied in many potential applications.