The role of the multifunctional antimicrobial peptide melittin in gene delivery

Melittin is vital for the endosomal escape of nanoparticles, but its excessive cytotoxicity in mammalian cells limits its value as a potential therapeutic agent. Several novel analogs of melittin have been optimized and characterized to establish a non-toxic melittin-based gene delivery system, in which the sequences of the melittin peptides were altered to reduce their cytotoxic activity. This review focusses on the involvement of melittin in nanoparticle endosomal escape and on the construction of melittin conjugates to boost gene delivery. Endosomal escape mechanisms for melittin, as well as the development of melittin as a therapeutic agent and its potential applications in nanomedicine, are discussed.