Self-Assembling Cyclic Peptide Nanotubes for the Delivery of Doxorubicin into Drug-Resistant Cancer Cells

Synthetic antimicrobial cyclic peptides conjugated to an antitumoral drug are used against drug-resistant cancer cells for a combined drug delivery strategy. The antimicrobial peptides are based on nanotube-forming cyclic peptides of alternating chirality, whose amphipathic and cationic characteristics determine their propensity to mainly interact with cell membranes rich in anionic phospholipids. This affinity triggers the formation of a supramolecular structure capable of destabilizing cell membranes such as those present in endosomes, thereby facilitating the delivery of the therapeutic agent to the cell nucleus and circumventing the cellular resistance mechanisms associated with efflux pumps.