The development of smart and controlled nanocarriers for targeted and triggered drug delivery provides therapeutic opportunities for the treatment of major diseases such as infections, inflammation, and cancer. Synthetic amphiphilic copolymers, able to undergo self-assembly into nanostructures, are ideal carriers for drug delivery due to the flexibility and diversity of polymer chemistry. Various carrier morphologies can be engineered with tuneable stabilities and surface chemistries, which include facile functionalisation with targeting ligands, in addition to triggerable drug release via stimuli-responsive copolymers. Typical morphologies of polymer-based structures used for drug delivery include micelles (spherical and worm-like), vesicles (polymersomes), capsules, polyion complex (PIC) micelles and vesicles, nanoparticles, and nanogels. The key advantages offered by nanogels are their ease of preparation that yields uniform and tuneable sizes, relatively high encapsulation efficiency, stability in the presence of serum, and the possibility of simple introduction of stimuli responsiveness. To yield high level of control of drug loading and triggered release, temperature and/or enzyme-responsive motifs can be incorporated in polymer-based drug delivery. With respect to temperature-triggered systems, poly(N-isopropylacrylamide) (PNIPAM) remains one of the most studied polymers incorporated in the design of temperature-responsive materials for biomedical applications due to its fast temperature-induced phase transition at a lower critical solution temperature (LCST) of ~32 °C. Copolymers of PNIPAM with a temperatureindependent hydrophilic block allow rapid assembly of nanostructures upon heating either after or during the polymerisation because of the thermally induced collapse of the PNIPAM block at temperatures above the LCST. However, PNIPAM-based nanoassemblies are limited to transition around 32 °C; the LCST cannot be changed easily. Further, temperature is not an ideal trigger for cargo release given our fixed body temperature. Hence, modulation of the self-assembly temperatures (LCST) using a range of different copolymers, combined with a suitable stimuli-responsive cross-linking strategy, represents an interesting alternative platform that could be employed both above and below the LCST.