Innovative Approaches of Engineering Tumor-Targeting Bacteria with Different Therapeutic Payloads to Fight Cancer: A Smart Strategy of Disease Management

Abstract

Conventional therapies for cancer eradication like surgery, radiotherapy, and chemotherapy, even though most widely used, still suffer from some disappointing outcomes. The limitations of these therapies during cancer recurrence and metastasis demonstrate the need for better alternatives. Some bacteria preferentially colonize and proliferate inside tumor mass; thus these bacteria can be used as ideal candidates to deliver antitumor therapeutic agents. The bacteria like Bacillus spp., Clostridium spp., E. coli, Listeria spp., and Salmonella spp. can be reprogrammed to produce, transport, and deliver anticancer agents, eg, cytotoxic agents, prodrug converting enzymes, immunomodulators, tumor stroma targeting agents, siRNA, and drug-loaded nanoformulations based on clinical requirements. In addition, these bacteria can be genetically modified to express various functional proteins and targeting ligands that can enhance the targeting approach and controlled drug-delivery. Low tumor-targeting and weak penetration power deep inside the tumor mass limits the use of anticancer drug-nanoformulations. By using anticancer drug nanoformulations and other therapeutic payloads in combination with antitumor bacteria, it makes a synergistic effect against cancer by overcoming the individual limitations. The tumor-targeting bacteria can be either used as a monotherapy or in addition with other anticancer therapies like photothermal therapy, photodynamic therapy, and magnetic field therapy to accomplish better clinical outcomes. The toxicity issues on normal tissues is the main concern regarding the use of engineered antitumor bacteria, which requires deeper research. In this article, the mechanism by which bacteria sense tumor microenvironment, role of some anticancer agents, and the recent advancement of engineering bacteria with different therapeutic payloads to combat cancers has been reviewed. In addition, future prospective and some clinical trials are also discussed.

Magnetothermal Control of Temperature-Sensitive Repressors in Superparamagnetic Iron Nanoparticle-Coated Bacillus subtilis

“…This would comprise a modular platform as the basis for developing a variety of potential therapeutics. Directed delivery and targeted activation offer the potential to improve therapeutic effects and reduce toxicity of bacteriotherapies while imaging can guide development of bacteriotherapies by assessing delivery, retention, and activation within the target tissue . Here, we use magnetic hyperthermia and imaging to develop SPION-coated B. subtilis as a system of controlled bacterial gene expression for use in bacteriotherapies.…”

Magnetothermal control of temperature-sensitive repressors in superparamagnetic iron nanoparticle-coatedBacillus subtilis

“…Directed delivery and targeted activation can improve therapeutic effects and reduce toxicity of bacteriotherapies while imaging can guide development of novel bacteriotherapies by assessing delivery, retention and activation within the target tissue. 68 Here we use magnetic hyperthermia and imaging to characterize the use of superparamagnetic nanoparticle-coated B. subtilis as a new approach for controlling Gram-positive bacterial gene expression with potential use in bacteriotherapies.…”

Emulating interactions between microorganisms and tumor microenvironment to develop cancer theranostics

“…18 F-FDS) as food granules could be employed in tumor monitoring and imaging 57 . The flagella and LPS in the cell wall are mediators for different immune cells, including CD8+ T cells, Treg cells, macrophage, NK cell and dendritic cells in TME 58 (Figure 2 C) .…”

“…Fungi only present cytotoxicity because their structure contains multiple polysaccharides 176 , but protozoa only interact directly with tumor cells by expressing tumor-targeting proteins 71 . In summary, the tumor-targeting effects of microorganisms are based on certain receptors on tumor cells 58 , 71 , 119 , and the cytotoxic effects can be attributed to the stimulation of apoptotic (caspase 3/7, Bcl2, MAPK etc.) and autophagic pathways in tumor cells 53 , 155 , 184 .…”