A biomimetic nanoreactor for combinational chemo/chemodynamic therapy of choriocarcinoma through synergistic apoptosis and ferroptosis strategy

Choriocarcinoma is a malignant tumor caused by aberrant proliferation and excessive invasion of trophoblastic cells in the uterus. Treatment for choriocarcinoma is hampered by severe side effects and drug resistance caused by insufficient delivery of chemotherapeutics. This dilemma can be solved by a novel approach of nanoparticlebased antineoplastic drug delivery through homologous targeting. Therefore, we developed a cancer cell membrane-coated biomimetic nanoreactor (MMC) built on a ferric metal-organic framework (MIL-100) encapsulating methotrexate (MTX) to achieve maximum therapeutic effects with negligible side effects. MMC could specifically target tumor cells and accumulate within tumor sites. MMC showed significant anticancer effects on JEG-3 cells, including inhibiting cell proliferation by cell cycle arrest at G0/G1 stage, and reducing endocrine function and migration ability. Furthermore, & BULL;OH overproduction by the Fenton reaction caused apoptosis and remarkable chemodynamic therapy (CDT) effects, glutathione scavenging led to intracellular redox dyshomeostasis and lipid peroxidation resulted in ferroptosis. In vivo studies demonstrated satisfactory tumor inhibition effects on tumor-bearing mice without appreciable toxicity. Further transcriptomics analysis revealed that MMC influences multiple pathways in cancer and cell death, including apoptosis and ferroptosis. This elaborately synthesized biomimetic nanoreactor offers a multifunctional reference for cancer therapy by presenting a new strategy for combining chemotherapy with CDT through synergistic apoptosis and ferroptosis.