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

Abstract

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. Cancer therapy can be challenging because numerous anticancer medications impact both healthy tissues and malignant cells. This can result in adverse effects and might lower the amount of drug that penetrates a tumor. Consequently, investigators are developing novel methods to deliver cancer therapies more precisely. Bacterial ghosts (BGs) are vacuous structures formed when researchers extract bacteria’s internal components. Because they preserve their external structure, these shells can transport pharmaceuticals and other biological substances while also engaging the immune system. This makes them potentially advantageous for administering cancer therapies directly to tumors. This review summarizes contemporary studies on using BGs to deliver various cancer therapies, including chemotherapeutic agents, proteins, genetic materials, and other bioactive compounds. Research in laboratory and animal models indicates that BGs can enhance drug transport, amplify the efficacy of some therapies, and provoke immune responses against cancer. Researchers can also modify them to more specifically identify cancer cells or to release their contents in a regulated manner. Nonetheless, BG technology is still in its nascent phase. Key challenges include reliable mass production, long-term storage stability, efficient drug loading, and safety assurance. More robust data from well-designed animal experiments and, ultimately, clinical trials are needed. Overall, BGs are a promising strategy for cancer therapy; however, further investigation is needed before their safe, routine use in patients.

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