Glutathione-Triggered Mitochondria-Targeting Reassembly from Polymeric Micelles to Nanofibers for a Synergistic Anticancer Effect.

Nanofibers self-assembled from peptides have attracted much attention to inhibit cancer cells. However, there are still some disadvantages, including high concentration for self-assembly and incapability to load drugs, which limit their applications. In this report, we rationally integrate self-assembled peptides, glutathione-sensitive disulfide bonds, and mitochondrial targeting moieties into the amphiphilic block copolymer to construct the nanocarriers, which can be used to load anticancer drug doxorubicin (DOX). After cellular internalization, the nanocarriers can reassemble from micelles to nanofibers under the trigger by glutathione and locate in mitochondria. The released DOX and nanofibers induce mitochondrial dysfunction and activate the apoptosis pathway to synergistically inhibit tumor cells. This organelle-specific drug delivery system with reassembly capability from micelles to nanofibers shows great potential for effectively killing cancer cells.