Truncated ferritin nanocages: enhanced drug encapsulation and delivery

Nanomedicine has emerged as a promising strategy to mitigate the drawbacks of chemotherapy by enabling targeted drug delivery. Protein nanocages, particularly ferritin, have gained attention due to their unique structural properties and biocompatibility. Herein, the development and characterization of truncated maize ferritin 1 (T-ZmFer1) nanocages for enhanced drug delivery are reported, achieved by removing the E-helix through excision of 17 amino acids from the C-terminus of the protein. T-ZmFer1 was expressed in Escherichia coli Bl21 (DE3) and optimized to enhance soluble protein expression. Purified T-ZmFer1 nanocages exhibited a size of 18.17 nm with a zeta potential of −19.9 mV, indicating well-defined structural characteristics. Drug encapsulation studies revealed a significant increase in encapsulation capacity for T-ZmFer1 nanocages compared to intact ZmFer1 nanocages, with a loading efficiency of ≈76 DOX/protein. Moreover, in vitro drug release profiles demonstrated controlled release kinetics for T-ZmFer1 nanocages, with pH-dependent release behavior. Cytotoxicity assays in SKBR3 cells showed comparable efficacy between DOX-loaded T-ZmFer1 and ZmFer1 nanocages, with T-ZmFer1 nanocages exhibiting superior cytotoxicity at 1 μM DOX concentration. This study underscores the potential of T-ZmFer1 nanocages as versatile drug delivery systems for cancer therapy, offering enhanced biocompatibility and therapeutic efficacy, thus contributing to the advancement of nanomedicine.