Recently, the team led by Shen Qi at the School of Pharmacy, Shanghai Jiao Tong University, published a study in the Journal of Controlled Release, entitled “Outer membrane vesicle-coated ferrocene nanoparticles induce dual ferroptosis for cancer immunotherapy.” This work, for the first time, constructed outer membrane vesicle–coated biomimetic ferrocene nanoparticles (FMV@PCFPC) that, through synergistic action, induce dual ferroptosis and offer a new paradigm for antitumor immunotherapy
Fusobacterium nucleatum (Fn), a common intratumoral anaerobe, can secrete virulence factors that suppress the cytotoxic function of CD8⁺ T cells, reduce immune cell infiltration, and promote the progression of breast cancer. Among existing treatments, antibiotics readily induce metabolic disorders and bacterial resistance, while tumor-targeting nanomedicines have difficulty acting on both bacteria and tumor cells simultaneously, limiting therapeutic efficacy. Therefore, breaking the immunosuppressive environment within tumors has become key to improving the therapeutic outcome of breast cancer.
In this study, the authors designed the FMV@PCFPC system to realize, via multicomponent synergy, a complete therapeutic chain of “targeted delivery–dual ferroptosis–immune activation.” The roles of each component are as follows: ① Tumor-targeting advantage: FMV is a natural vesicle secreted by Fn., and its surface is rich in specific adhesion proteins that can bind to adhesion receptors on the surface of breast cancer cells, achieving precise targeting of tumor tissues. ② Induction of dual ferroptosis: ferrocene in the nanoparticles serves as a stable Fe²⁺ donor that generates ·OH via the Fenton reaction, providing the “fuel” for dual ferroptosis in tumors and intratumoral bacteria; cinnamaldehyde can undergo a Michael addition reaction with GSH, lowering GSH levels in tumor cells and bacteria and removing resistance to ferroptosis; at the same time, cinnamaldehyde can directly disrupt bacterial cell membranes and inhibit biofilm formation, synergizing with Fe²⁺ to enhance antibacterial effects. ③ Efficient immune activation: FMV carries pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), promoting DC maturation and cytokine secretion and enhancing immune responses. Meanwhile, tumor ferroptosis triggers immunogenic cell death (ICD), activating DCs and promoting antigen presentation, thereby inducing specific T-cell responses and ultimately forming durable antitumor immune memory.
Figure 1. Schematic of FMV@PCFPC preparation and immune activation mechanism
In summary, this study for the first time constructed outer membrane vesicle–coated biomimetic nanoparticles, FMV@PCFPC, which, through synergistic action, achieve efficient clearance of tumors and intratumoral bacteria via dual ferroptosis, providing a new idea for lifting tumor immunosuppression.
The first author of this study is Ziqi Shen, a master’s student at the School of Pharmacy, Shanghai Jiao Tong University, and the corresponding author is Researcher Qi Shen
Paper link: https://doi.org/10.1016/j.jconrel.2025.114203
Author: Qi Shen
Contributing Unit: School of Pharmacy
Translate: Rui Su
Proof: Steven
