Mesoporous silica nanoparticles with cyclic peptide gatekeeper for stimulus-responsive drug release by conformational transformation

For the preparation of drug delivery vehicles, peptides have been widely adopted due to their valuable bioresponsiveness. In addition, the conformational change of peptides in response to a particular bioenvironment could be adopted as a talented motif for the on-demand release of loaded cargos in mesoporous silica nanoparticles. Here, a cyclic peptide gatekeeper with an intramolecular disulfide bond for on–off triggered gatekeeping and NEWQG sequence for selective binding is prepared. The cyclic peptide gatekeeper conjugated onto the surface of mesoporous silica nanoparticles completely blocks the undesirable leakage of loaded cargos in the pore. Upon treatment of biological reducing agent, the entrapped drugs in the pore of the nanoparticles are released selectively over time by specific reduction of the cystine unit and thereby conformational transformation of the peptide gatekeeper. Graphical abstract