Redox degradable 3-helix micelles with tunable sensitivity

We report a new design of redox-responsive 15 nm 3-helix micelles with tunable cargo release pathway. The self-assembled micelles are structurally stabilized by the 3-helix bundle forming peptide-poly(ethylene glycol) conjugates and exhibit excellent stability without the presence of reducing agent (e.g., glutathione). Incorporating disulfide linkers at different locations of peptide-poly(ethylene glycol) conjugates yields different redox-degradation products that enable different degradation kinetics of the micelle and subsequently cargo release pathway. In conjunction with other attributes of the 3-helix micelle such as small size, long circulation, and deep tumoral penetration, the present study provides an effective strategy toward controlled intercellular delivery of hydrophobic drugs and therapeutic peptides.