Figure 1.

Design and function of an ELP_BC nanopeptifier. (A) Each nanopeptifier is a ternary fusion of a therapeutic payload, an ELP_BC comprised of a hydrophobic and hydrophilic ELP domain, and a CPP. (B) At physiologic temperature (“off” state, 37 °C), nanopeptifiers are soluble unimers, displaying a single CPP on their hydrophilic terminus. At conditions of mild clinical hyperthermia (“on” state, 42 °C), nanopeptifiers self-assemble into spherical micelles, displaying a high density of CPPs on the micelle corona. The increased CPP density amplifies cellular uptake in the micelle state, as compared to the unimer state. Important nanopeptifier parameters include: leakage uptake, “off” state uptake at 37 °C; amplified uptake, “on” state uptake at 42 °C; gain, ratio of “on” to “off” state uptake.