A novel melanin complex displayed the affinity to HepG2 cell membrane and nucleus

Chitosan-melanin complex from Catharsius molossus L. has proven to possess superior pharmaceutical excipient performance and may be the new source of water-soluble protein-free natural melanin. Herein, it was enzymatically hydrolyzed into the chitooligosaccharide-melanin complex (CMC) whose main chemical units were composed of eumelanin and chitooligosaccharides and showed three-layer structures. Additionally, this biomacromolecule could self-assemble into 40 nm nanoparticles (CMC Nps) in a weakly acidic aqueous solution. Interestingly, CMC displayed strong affinity for cell membrane by binding the phosphatidylserine, glycoprotein, glycolipids and glycosaminoglycans accumulated on the surface of tumor cells, notably, CMC Nps could enter cells and mainly target the nucleus by interacting with DNA and/or RNA substrates located around the nucleus to disrupt the proliferation and apoptosis processes. The findings suggest CMC may be the novel material for subcellular organelle targeting of cancer cells.