Bacterial Ghosts as Innovative Transport Vehicles for Platinum-Based Anticancer Drugs

Cisplatin, carboplatin, and oxaliplatin (OXA) are widely used platinum-based anticancer drugs, but their clinical application is limited by severe adverse effects, including nephrotoxicity, ototoxicity, and neurotoxicity, as well as drug resistance. Oxaliplatin (Eloxatin) is the only platinum compound showing superior clinical efficacy in the treatment of colorectal cancer, yet its use is restricted by dose-dependent toxicity. To address these limitations, OXA and four derivatives were loaded into bacterial ghosts (BGs) as novel drug carriers. BGs derived from the nonpathogenic strains Escherichia coli Nissle 1917 (EcN) and Escherichia coli NM522 (Ec NM522) were loaded by simple resuspension and incubation. Platinum content was quantified by inductively coupled plasma mass spectrometry, while the physicochemical properties of the formulations were characterized by fast protein liquid chromatography, transmission and scanning electron microscopy, electron energy-loss spectroscopy, and flow cytometry. The stability of OXA-loaded BG formulations was evaluated in different media and under various storage conditions for up to 120 days. The formulations demonstrated high batch-to-batch reproducibility, and bacterial encapsulation preserved the in vitro anticancer activity of the platinum compounds.