| dc.description.abstract | Cancer remains a significant global health challenge, with traditional treatments like surgery, chemotherapy, and radiation often causing severe side effects. Bacterial-mediated cancer therapy is emerging as a promising alternative, though it faces challenges such as maintaining bacterial viability during sterilization and avoiding harmful endotoxin release. Researchers are exploring new drug delivery materials to enhance the efficacy of bacterial therapies, and Metal-Organic Frameworks (MOFs) have gained attention for their versatility and stability. This study demonstrates the encapsulation of E. coli within Zeolitic Imidazolate Framework-90 (ZIF-90), a type of MOFs. Encapsulating bacteria within ZIF-90 allows them to retain activity under UV sterilization and evade antibiotic attacks within the human body. Furthermore, this method prevents the bacteria directly exposed to the bloodstream, thereby avoiding a strong immune response .In vitro experiments showed that E. coli@ZIF-90 reduces the survival rate of breast cancer cells to 47%, attributed to lipopolysaccharides (LPS) on the bacterial membrane inducing inflammatory responses. Simultaneously, Western blot analysis verified that E. coli@ZIF-90 can induce pyroptosis in breast cancer cells. The expression levels of proteins involved in the pyroptosis pathway were significantly different in breast cancer cells treated with E. coli@ZIF-90 compared to the control group. In contrast, pyroptosis hasn’t been occured in normal cells. Using inductively coupled plasma mass spectrometry (ICP-MS), it was detected that the concentration of zinc ions in breast cancer cells after E. coli@ZIF-90 treatment reached up to 1.15 mg/L, compared to 0.43 mg/L in normal cells, showing a significant difference (P < 0.05). Microscopic observations revealed a significant difference (P < 0.0001) in the amount of internalized E. coli between breast cancer cells and normal cells after E. coli@ZIF-90 treatment. In vivo experiments confirmed that treatment with E. coli@ZIF-90 inhibited 72% of the cancer cell nodule area, underscoring the potential of ZIF-90 as a carrier in bacterial-mediated cancer therapy. In the acidic tumor environment, E. coli@ZIF-90 selectively releases bacteria that colonize the tumor in a hypoxic environment, inducing pyroptosis in cancer cells and activating the immune system to attack the tumor. This study offers innovative approaches that could lead to breakthroughs in cancer therapy.
In summary, encapsulating E. coli within ZIF-90 presents a novel and effective strategy for targeted bacterial-mediated cancer therapy, showing promising results both in vitro and in vivo. | en_US |