Application of Invasive Bacteria for the Delivery of Anti-cancer Therapeutics

Bacterial vectors for biomolecule delivery to targeted organelles, facilitating temporary or continuous protein production, have emerged as a promising approach for treating acquired and inherited diseases. This method offers a selective cancer eradication and targeting strategy with minimal side effects. Bacterial vectors provide an alternative to viral gene delivery, given their capacity to deliver large genetic materials while inducing minimal immunogenicity and cytotoxicity. Bacteria such as Bifidobacterium, Salmonella, and Clostridium have demonstrated potential for tumor-targeted biomolecule delivery. These vectors have also been used to transfer and amplify genes encoding biomolecules such as prodrug-converting enzymes, toxins, angiogenesis inhibitors, and cytokines. The microenvironment of necrotic tumors offers a unique opportunity for targeted therapy with the non-pathogenic anaerobic bacterium. For example, Clostridium sporogenes can germinate selectively in the necrotic regions upon injection as endospores, which helps to enhance the specificity of Clostridium sporogenes, resulting in tumor-specific colonization. Further, some invasive bacteria vectors engineered with the invasin gene from Yersinia Pseudotuberculosis, which enables specific binding to integrin receptors abundantly expressed in cancer cells and escape the endosome with incorporation of the Listeriolysin O gene from Listeria monocytogenes, have shown potential for application in cancer therapy. This review provides an overview of the use of the bacteria vector in cancer therapy, highlighting strategies to maximize delivery efficiency and address potential challenges.