Francesco Baschieri

Loading of Dicarboxylatoplatinum(II)‐NHC Complexes in Bacterial Ghosts as an Advanced Development in Cancer Therapy

ABSTRACT This study aimed to improve the drug‐like properties of benzimidazole‐based Pt(II)‐N‐heterocyclic carbene (NHC) complexes, particularly by enhancing their water solubility and delivery to cancer cells. Accordingly, four new Pt(II) complexes of the benzimidazol‐2‐ylidene type, featuring monodentate carboxylato ligands, were prepared and their structures confirmed through a combination of spectroscopic and crystallographic techniques. Their stability in aqueous solution and cell culture medium was investigated by 1 H NMR spectroscopy and HPLC‐MS analysis. Cytotoxicity was assessed using the MTT assay in ovarian cancer cell lines (A2780wt (cisplatin sensitive) and A2780cis (cisplatin resistant)) and a noncancerous bone marrow stromal cell line (HS‐5). Most complexes exhibited cytotoxicity comparable to or exceeding that of carboplatin, with preferential activity toward cancer cells. Loading of all four Pt(II) complexes into bacterial ghost cells (BGs) derived from two different nonpathogenic bacterial strains, Escherichia coli (E. coli) Nissle 1917 and E. coli NM522 notably enhanced the intracellular accumulation and cytotoxicity. Furthermore, mechanistic studies demonstrated that all tested compounds, regardless of formulation, induced apoptosis. Their potential to trigger immunogenic cell death was also evaluated, though only a modest effect was observed on selected hallmarks. Collectively, these findings highlight the potential of dicarboxylatoplatinum(II)‐NHC complexes, particularly loaded into BG‐based formulations, as promising anticancer drug candidates.

The Rab25‐ ADAMTS5 axis as a previously undescribed mechanism for sensing tumor microenvironment complexity

The tumor microenvironment (TME), particularly the extracellular matrix (ECM), plays a critical role in cancer progression. Focusing on ovarian cancer, Yuan et al. reveal an ECM‐dependent signaling axis where cancer‐associated fibroblasts (CAFs) enhance the invasiveness of cancer cells via Rab25‐driven upregulation of the protease ADAMTS5. This process is only triggered in the presence of native ECM. In turn, stimulated cancer cells favor CAF invasiveness through a mechanism that remains to be identified. These findings uncover a bidirectional crosstalk between cancer cells and CAFs and highlight the importance of context‐specific in vitro models to decipher ECM‐mediated tumor dynamics.