A Novel Insect Cuticle Peptide-Based Nano-Capsule Platform

Nano-capsules can be used to transport a variety of substances into eukaryotic cells. Herein, we develop a novel insect cuticle peptide (ICP)-based nano-capsule platform with the potential for cytosolic drug delivery applications. Originated from insect cuticular proteins, the ICPs can form hollow nano-sized capsules in mixed solvents, via an unusual liquid-liquid phase separation (LLPS) mediated self-assembly process. However, the underlying mechanism of ICP self-assembly remains unclear. By combining molecular dynamics (MD) simulations and biochemical experiments, we present the first study to unravel the mechanics of ICP self-assembly, and to demonstrate the tunability of ICP nano-capsules simply by controlling the peptide sequences. The successful co-delivery of hydrophilic and hydrophobic drugs with synergistic effects is confirmed experimentally. With this work, we aim to exemplify the potential of our ICP-based nano-capsule platform for important biomedical applications, such as drug delivery, cancer therapy and precision medicines.