Bacteria-Mediated Tumor Therapy Utilizing Photothermally-Controlled TNF-α Expression via Oral Administration

Abstract

Oral drug administration is widely adopted for diverse drugs and is convenient to use due to the capability of reaching different parts of the body via the bloodstream. However, it is generally not feasible for biomacromolecular antitumor drugs such as protein and nucleic acids due to the limited absorption through gastrointestinal tract (GIT) and the poor tumor targeting. Here, we report a noninvasive thermally sensitive programmable therapetic system using bacteria E. coli MG1655 as an vehicle for tumor treatments via oral administration. Thermally sensitive programmable bacteria (TPB) are transformed with plasmids expressing therapeutic protein TNF-α and then decorated with biomineralized gold nanoparticles (AuNPs) to obtain TPB@Au. AuNPs and TNF-α plasmids efficaciously protected by TPB in the gut can be transported into internal microcirculation via transcytosis of microfold cells (M cells). After that, the bacteria-based antitumor vehicles accumulate at tumor sites due to the anaerobic bacterial feature of homing to tumor microenvironments. In vitro and in vivo experiments verify the successful delivery of AuNPs and TNF-α plasmids by TPB. Importantly, under remote activation the expression of TNF-α in tumor sites can be procisely controlled by the heat generated from photothermal AuNPs to exert therapeutic actions. The biological security evaluation demonstrates that this strategy would not disturb the balance of intestinal flora.

Engineered Bacterial Bioreactor for Tumor Therapy via Fenton‐Like Reaction with Localized H2O2 Generation

“…Additionally, facultative anaerobe shows a tropism toward the tumor regions due to the hypoxic and eutrophic tumor microenvironment, which is reasoned by fast proliferative tumor cells and insufficient blood supply . Substantial research has utilized bacteria to transport functional nanoparticles with improved tumor‐targeting capability, including nano photosensitizer, up‐conversion nanoparticles (UCNPs), and photocatalytic nanoparticles, etc. As a consequence, engineered bacteria modified with nanoparticles could establish optimized platforms for synthetic biology …”

Improving Cancer Immunotherapy Outcomes Using Biomaterials

“…Many bacteria have the ability to target, and in some cases,e ven destroy tumors,a nd resulting cellular debris can serve as an atural adjuvant to trigger antitumor immunity. [33] Bacterial cytoplasmic membranes may be employed to target tumors or used as adjuvants for enhanced immunotherapy. [34] Growing evidence suggests that the microbiome can influence diverse human diseases,i ncluding cancer.…”

An RGB-emitting molecular cocktail for the detection of bacterial fingerprints

“…1 With our in-depth understanding of the critical relationship between microbes and diseases, the study of commensal microbes is currently in the spotlight. [2][3][4][5][6][7] For example, Fusobacterium nucleatum, a bacterium that exists in the gut, can be viewed as a biomarker for colorectal cancer (CRC) diagnosis. 8 Some specic oral bacteria, including Capnocytophaga gingivalis, Prevotella melaninogenica, and Streptococcus mitis, have been found to predict 80% of oral squamous cell carcinoma (OSCC) cases.…”