Bacterial ghosts: next-generation biological platforms for targeted cancer therapy and immunomodulation

Bacterial Ghosts (BGs) are a promising biological platform for cancer drug delivery, addressing critical issues such as toxicity, poor bioavailability, and off-target effects. These empty bacterial envelopes retain native surface structures and immunostimulatory properties, serving as both drug carriers and adjuvants. This review synthesizes current evidence on BG production, immunological properties, and their application in delivering chemotherapeutics, nucleic acids, proteins, and other bioactives across colorectal, lung, breast, and lymphoma models. Preclinical studies show improved tumor targeting and therapeutic efficacy by leveraging passive mechanisms and active surface engineering. However, significant translational hurdles remain: suboptimal loading efficiency, challenges in large-scale manufacturing and batch-to-batch reproducibility, unclear storage stability, and unresolved biosafety concerns. While emerging combination strategies and stimuli-responsive release systems offer potential solutions, systematic biodistribution and long-term safety evaluations are critically lacking. The authors conclude that BGs are a versatile and potent delivery system, but clinical application requires optimized production, surface functionalization, and rigorousin vivo validation in clinically relevant models. Overall, this review summarizes current research and future directions for BG-based cancer therapies.