Design and function of an ELPBC nanopeptifier. (A) Each
nanopeptifier is a ternary fusion of a therapeutic payload, an ELPBC 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.