Spatio-temporally tailoring cell–material interactions is essential for developing smart delivery systems and
intelligent biointerfaces. Here we report new photo-activatable cell–material interfacing systems that
trigger cellular uptake of various cargoes and cell adhesion towards surfaces. To achieve this, we
designed a novel photo-caged peptide which undergoes a structural transition from an antifouling ligand
to a cell-penetrating peptide upon photo-irradiation. When the peptide is conjugated to ligands of
interest, we demonstrate the photo-activated cellular uptake of a wide range of cargoes, including
small fluorophores, proteins, inorganic (e.g., quantum dots and gold nanostars) and organic
nanomaterials (e.g., polymeric particles), and liposomes. Using this system, we can remotely regulate
drug administration into cancer cells by functionalizing camptothecin-loaded polymeric nanoparticles
with our synthetic peptide ligands. Furthermore, we show light-controlled cell adhesion on a peptidemodified surface and 3D spatiotemporal control over cellular uptake of nanoparticles using two-photon
excitation. We anticipate that the innovative approach proposed in this work will help to establish new
stimuli-responsive delivery systems and biomaterials