Water-soluble macromolecular chain transfer agents (Macro-CTAs) were developed for the microwave-assisted precipitation polymerization of N-isopropylacrylamide. Two types of Macro-CTAs, amphiphilic (Macro-CTA1) and hydrophilic (Macro-CTA2), were investigated regarding their activity for the facile formation of nanoparticles and double hydrophilic block copolymers by RAFT processes. While both Macro-CTAs functioned as steric stabilization agents, the variation in their surface activity afforded different levels of control over the resulting nanoparticles in the presence of cross-linkers. The cross-linked nanoparticles produced using the amphiphilic Macro-CTA1 were less uniform than those produced using the fully hydrophilic Macro-CTA2. The nanoparticles spontaneously formed core-shell structures with surface functionalities derived from those of the Macro-CTAs. In the absence of cross-linkers, both types of Macro-CTAs showed excellent control over the RAFT precipitation polymerization process with well-defined, double hydrophilic block copolymers being obtained. The power of combining microwave irradiation with RAFT procedures was evident in the high efficiency and high solids content of the polymerization systems. In addition, the "living" nature of the nanoparticles allowed for further copolymerization leading to multiresponsive nanostructured hydrogels containing surface functional groups, which were used for surface bioconjugation.