Living-System-Driven Evolution of Self-Assembled-Peptide Probes: For Boosting Glioma Theranostics.

The primary principle for new molecular evolution is from nature, mimicking nature, and beyond nature, since it is extremely important for the artificial molecules to keep their structure and function in the natural system. It is especially true for the self-assembled supramolecular construction in situ in complicated living bodies. Herein, we put forward a directed evolution strategy consisting of high-content screening from the living system and artificial modification in order to find "totipotential peptides" in a precise way. Progressive dimension reduction of the capability and precise anchoring of the target were realized. Through the living system evolution, we obtain a glioma-targeting and living system-induced self-assembled leading compound CCP. Through the artificial evolution, CCP was further stapled and was hydrophobically modified as NSCCP2, which demonstrated stability and NIR-II emission characteristics. NSCCP2 could realize high-resolution molecular imaging and therapy simultaneously. We envision that the strategy and its applications provide a new method for molecular discovery and improve the performance of peptide nano-self-assemblies for diagnostics and therapy.