Encapsulation of (NHC)-Pt(II) complexes in bacterial ghosts as an advanced method in cancer therapy

Cancer treatments include chemotherapy, among which platinum-based chemotherapy drugs like Cisplatin are effective but limited by severe side effects and drug resistance. Second-generation drugs like Oxaliplatin, which also form platinum-DNA adducts to induce cell death, were developed to overcome these issues. In 2010, oxaliplatin was found to trigger immunogenic cell death (ICD) in colon cancer cells, activating immune responses through DAMPs such as calreticulin and HMGB1.
Bacterial ghosts (BGs), which are gram-negative bacteria emptied of cytoplasmic content while retaining their surface properties, can also induce ICD and serve as immune adjuvants or drug delivery vehicles. These properties make them suitable for encapsulating and delivering peptides, foreign DNA, or drugs. Building on this, Groza et al. proposed combining oxaliplatin with probiotic BGs to treat colorectal cancer. Expanding this idea, we have developed four novel platinum(II)-N-heterocyclic carbene (NHC) complexes  encapsulated in two strains of BGs (E. coli NM522 and E. coli Nissle 1917). These compounds were synthesized and characterized for stability via RP-HPLC, then tested for cytotoxicity against A2780 ovarian carcinoma cells in their free and encapsulated forms via an MTT assay. Further evaluation included ICD induction, intracellular DNA damage with a comet assay and cellular uptake analyzed by atomic absorption spectroscopy. Encapsulation in BGs enhanced cytotoxicity, cellular uptake, and apoptosis/ICD induction, highlighting the potential of encapsulated NHC-Pt(II) complexes, particularly in E. coli NM522, as a novel anticancer drug delivery method.