Stimulus‐Induced Conformational Transformation of a Cyclic Peptide for Selective Cell‐Targeting On–Off Gatekeeper for Mesoporous Nanocarriers

αvβ3 Integrin is upregulated on many cancer cells. We designed a dual functional cyclic peptide gatekeeper with a capability of stimuli‐responsive conformational transformation which could serve as a selective cell‐targeting on–off gatekeeper for mesoporous nanocarriers. The advantage of employing the motif of stimuli‐induced conformational transformation of cyclic peptides is that they could be utilized not only as an on–off gatekeeper for the triggered release of cargo drugs but also as a targeting ligand of the carriers to desired cells with their respective binding receptors. The peptide gatekeepers on the surface of nanocarriers exhibited on–off gatekeeping via conformational transformation triggered by intracellular glutathione levels of the cancer cells. The cyclic RGD sequence of the peptide gatekeepers enhanced the intracellular uptake into tumor cells (A549) and the therapeutic efficacy of the nanocarrier. The other side of the gate: A dual‐functional cyclic peptide gatekeeper with a capability of stimuli‐responsive conformational transformation is reported which could serve as a selective cell‐targeting on–off gatekeeper for mesoporous nanocarriers.