Cell-selective intracellular drug delivery using doxorubicin and α-helical peptides conjugated to gold nanoparticles

Cell penetrating peptides (CPPs), which can enter a cell through the cell membrane, have potential research applications in the fields of drug delivery, gene therapy, and cancer therapy. However, CPPs are associated with problems such as low cell selectivity, low cell penetrating activity, and cell toxicity. To overcome the disadvantages of CPPs, we constructed a drug delivery system by developing 25 nm gold nanospheres (GNSs) conjugated to four α-helical CPPs from our peptide library. We examined the applicability of this cell-selective drug delivery system by evaluating its cell-penetrating and cell death activities and comparing them with those activities of the TAT peptide. Using the 25 nm GNS, we obtained higher cell death induction activity by the anti-cancer drug doxorubicin compared with our previous study using a 41 nm GNS. After entering the cell, the peptide-conjugated 25 nm GNS accumulated around the cell nucleus. High cell selectivity by α-helical CPP sequences was also demonstrated. Our results indicate that these α-helical peptide and 25 nm GNS conjugates are useful elements in an efficient cell-selective drug delivery system.