Nonlinear amplification of nano bowl surface concavity on the critical response threshold to biosignals

Abstract Polymer nanoparticles that can sharply sense and detect biological signals in cells are promising candidates for biomedical and theranostic nanomaterials. However, the response ability of current polymer assemblies poorly matches the requirement of trace concentration level (10−6 ~ 10−9 mol/L) of cellular biosignals due to their linear signal input-to-function output mode, which impedes their practical applications in vivo. Here we report a kind of nanobowl system with pH-tunable invaginated morphology that can nonlinearly amplify the response abilities toward biosignals by modulating the surface concavity. Compared to conventional spherical nanoparticles, nonspherical nanobowls with a specific concave structure reduce the critical response threshold of polymers by up to 5 orders of magnitude, from millimole to nanomole level, covering most of biosignal concentration windows. Moreover, we find that this nonlinear signal gain effect is originated from the collective impact of a single signal on transitioning the polymer chain aggregation state of individual assemblies, rather than just altering a certain unit or chain. This nonlinear signal-to-response mechanism is potential to solve the tricky problems of probing and sensing endogenous signals with trace physiological concentration.