Here we show 2'-deoxyguanosine derivatives that self-assemble in aqueous media into discrete supramolecular hexadecamers and exhibit the lower critical solution temperature (LCST) phenomenon. Spectroscopic, calorimetric, and electron microscopy studies support the fact that above the transition temperature (T(t)) the supramolecules further assemble into nanoscopic spherical globules of low polydispersity. Furthermore, the T(t) can be tuned to higher values by the addition of a more hydrophilic derivative. These findings uncover a new paradigm in the development of smart thermosensitive materials with properties and applications complementary to those of polymers.