Specific HER2 targeting and triggered drug release by conformational transformation of a dual-functional peptide gatekeeper on mesoporous nanocontainers

The HER2 receptor, highly expressed on the surface of about 30% of breast cancer cells, plays an important role in the development of various aggressive types of breast cancer. For specific targeting of HER2 and triggered drug release by stimuli-responsive conformational transformation, we developed a dual-functional cyclic peptide gatekeeper containing a HER2-binding sequence and an intramolecular disulfide bond on the surface of mesoporous nanocontainers. Without any stimuli, the release of entrapped drug in the mesopore of the nanocontainers was fully blocked. Upon addition of glutathione (GSH), the cargo drug was released by GSH-induced reduction of an intramolecular disulfide bond and thereby a conformational transformation from a cyclic to a linear form. Furthermore, the nanocontainers with a cyclic peptide gatekeeper showed enhanced intracellular uptake and selective therapeutic efficacy on HER2 positive SK-BR-3 cells.