A promising platform of hypoxia sensitive magnetosomes in hepatocellular carcinoma therapy.

Here, we engineered hypoxia-responsive nanoparticles (NI-HA-BMs-DOX) comprising 2-nitroimidazole (NI), hyaluronic acid (HA), bacterial magnetosomes (BMs), and doxorubicin (DOX) for targeted drug delivery. Under tumor hypoxia, the hypoxia-sensitive NI moiety undergoes reduction to 2-aminoimidazole, inducing a transition of the nanoparticles from a hydrophobic to a hydrophilic state, thereby facilitating controlled DOX release. Cellular assays demonstrated selective DOX delivery to HepG2 hepatocellular carcinoma cells under hypoxic conditions, while exhibiting minimal cytotoxicity toward normal hepatocytes (HL-7702). NI-HA-BMs-DOX significantly enhanced tumor cytotoxicity and apoptosis by upregulating caspase-3, caspase-8, and Tp53, demonstrating superior efficacy compared to free DOX and HA-BMs-DOX. In vivo studies further confirmed the therapeutic potential of NI-HA-BMs-DOX (4 mg/kg DOX equivalent), achieving a tumor inhibition rate of 55.38%, which exceeded that of HA-BMs-DOX (43.88%) and free DOX (34.90%). These findings validate NI-HA-BMs-DOX as a promising hypoxia-targeted therapeutic platform for HCC and highlight the potential of bacterial magnetosomes in improving drug delivery strategies for cancer treatment.