Nature Sub-Journal: Transforming bacteria into a drug delivery system is expected to overcome solid solid tumors

Source | Innovia Cancer As the "number one killer" threatening human health, cancer cells are a type of extremely tenacious cell.
They evade the body's immune system through a variety of ways, continue to proliferate and spread to expand their living space, and continue to mutate.
To generate heterogeneity so as not to be swept away
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These characteristics make cancer one of the most difficult to cure diseases
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So far, it has been difficult to penetrate solid tumor cell membranes, so it has not been able to effectively target key cancer pathways
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Current delivery methods, such as lipid nanoparticles, cell-penetrating peptides, and antibody-drug conjugates, are degraded due to their poor ability to enter cells, their inability to specifically target cancer cells, and their natural protection from invaders.
Therefore, the efficacy is limited
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On October 21, 2021, researchers from the University of Massachusetts and Ernest Pharmaceuticals published a research paper titled: Intracellular delivery of protein drugs with an autonomously lysing bacterial system reduces tumor growth and metastases in Nature Communications
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The research developed a non-toxic, bacteria-based delivery system-Salmonella, which not only can easily enter cells, but also can specifically target cancer cells to directly deliver proteins (drugs) without affecting healthy cells
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Once its protein payload is delivered, the bacteria will be eliminated, which can provide effective targeted therapy for cancers that are currently untreatable, such as liver cancer or metastatic breast cancer
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The delivery system uses a highly modified Salmonella strain.
The strain uses three gene circuits to precisely control drug production, cell invasion and protein release.
This use of Salmonella's natural invasion and survival mechanism can enable therapeutic proteins to directly and autonomously accumulate into cancer.
In the cell
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Early studies have shown that Salmonella will accumulate in tumors, but it is not known that they will invade cancer cells
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Researchers injected bacteria into mice and used fluorescence technology to accurately measure this cell penetration.
The study found that 70% of Salmonella can invade cancer cells
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70% of Salmonella can infiltrate cancer cells.
After the bacteria infiltrate the cancer cells, when Salmonella lyses for the first time, the payload protein is released into the cancer cells.
Over time, the protein is dispersed into the cytoplasm, where it can interact with the target.
Interaction
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In the mouse model, the researchers tested liver cancer and triple-negative breast cancer
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In breast cancer, after 14 days of treatment, the volume of breast tumors in mice was reduced by two times compared with the control group, and the growth of established metastases in the lungs was prevented
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Breast cancer treatment In two liver cancer models (BNL-MEA and Hepa), intravenous injection of Salmonella vector reduced the growth of the two liver cancer tumors by 47% and 57%.
After 50 days of treatment, no toxic effects were observed
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And completely eliminated the tumor in one mouse, and the mouse remained disease-free for more than 300 days
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Liver cancer treatment At present, 840,000 patients are diagnosed as unresectable hepatocellular carcinoma every year.
There is no curative treatment method, which can only improve the survival rate to a limited extent
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Treatment with Salmonella may be safer and more effective
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Seven days after the injection, Salmonella was cleared from most organs
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In addition, the delivered protein was not detected in healthy tissues, and toxicity was not observed
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The efficacy in a metastatic breast cancer model indicates that Salmonella reduces tumor growth and prevents metastasis, and can be used to treat advanced disease
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In summary, these results indicate that this Salmonella-based delivery platform is an effective cancer therapy, which can provide effective targeted therapy for currently incurable cancers, such as liver cancer or metastatic breast cancer, and improve the effectiveness of cancer treatment.
Sex and safety
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Link to the paper: https://