Cu1-catalyzed alkyne–azide and Diels–Alder “click” reactions are used in sequence, in a layer-by-layer build-up of dendrimers which undergo retro-Diels–Alder disassembly upon heating.
A simple and versatile dendrimer based platform to deliver therapeutic agents at temperatures within the physiological range, is reported. Lipoic acid conjugated at the periphery of the thermosensitive dendrimer formulations undergoes slow and sustained release at 37–42 °C, and rescues the cells from oxidative stress and a pro-inflammatory endotoxic agent.