A May 27, 2024 Nanowerk Spotlight article by Michael Berger features research into using bacteria as a delivery device for medical treatment, Note: Links have been removed,
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Researchers have long sought to harness bacteria as a Trojan horse to deliver therapeutic payloads deep into tumors. Certain species of bacteria preferentially grow in the hypoxic cores of solid tumors, enabling much deeper penetration than possible with standard nanomedicine drug delivery approaches that rely on passive accumulation. Additionally, some bacteria naturally produce substances toxic to cancer cells. However, maintaining control over bacterial replication and toxicity while achieving a meaningful anti-tumor effect has proven challenging.
Now, scientists from Shanghai University in China report (Advanced Functional Materials, “Engineering Photothermal and H2S-Producing Living Nanomedicine by Bacteria-Enabled Self-Mineralization”) an innovative strategy to engineer a hybrid bacterial-nanoparticle system dubbed “Sa@FeS” to launch a multi-pronged attack against tumors from within.
They start with an attenuated strain of Salmonella typhimurium bacteria, which is drawn to the hypoxic regions in tumors. By feeding the Salmonella specific nutrients, they coax it to biomineralize its cell surface with photothermal iron sulfide nanoparticles without impairing bacterial viability and mobility.
The resulting nanomedicine platform enables three distinct but synergistic therapeutic mechanisms. First, the Salmonella bacteria naturally produce hydrogen sulfide gas, which recent studies show can be directly toxic to cancer cells by damaging DNA, disrupting mitochondrial function, and inhibiting cellular metabolism. Second, upon exposure to near-infrared laser light, the iron sulfide nanoparticles efficiently convert the light to heat, subjecting tumor cells to photothermal ablation.
Most powerfully, the released hydrogen sulfide gas, mildly acidic tumor microenvironment, and photothermal heating work in concert to dramatically amplify the effectiveness of chemodynamic therapy. In this therapy, iron-based nanoparticles convert hydrogen peroxide into highly toxic hydroxyl radicals.
While promising, chemodynamic therapy is often limited by insufficient hydrogen peroxide in tumors. The Sa@FeS therapy overcomes this by using the released hydrogen sulfide to suppress tumor cells’ enzymes that break down hydrogen peroxide, causing its levels to build up. Simultaneously, the heating and acidosis accelerate the iron-catalyzed conversion of hydrogen peroxide to hydroxyl radicals.
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Berger’s May 27, 2024 article goes on to describe this new treatment’s advantages and finishes the article with scientists’ hopes that other microorganisms could be harnessed for treatments in the future, Note: Links have been removed,
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Moreover, the researchers suggest that beyond bacteria, other diverse microorganisms such as fungi and viruses could potentially be engineered for similar therapeutic applications, opening up an even broader horizon for ‘living medicines’. Nevertheless, this impressive study lights the way for a new generation of bio-inspired therapies that merge the tools of synthetic biology and nanotechnology to open new fronts in the war against cancer.
On that note, my July 2, 2024 post about a new approach to ending the global amphibian pandemic, features the proposed use of a virus to kill off the fungal infection affecting frogs.
Getting back to nanomedicine and synthetic biology, here’s a link to and a citation for the paper featured in Berger’s article.,
Engineering Photothermal and H2S-Producing Living Nanomedicine by Bacteria-Enabled Self-Mineralization by Weiyi Wang, Jun Song, Weijie Yu, Meng Chen, Guangru Li, Jinli Chen, Liang Chen, Luodan Yu, Yu Chen. Advanced Functional Materials DOI: https://doi.org/10.1002/adfm.202400929 First published: 14 May 2024
This paper is behind a paywall.