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| Nanomaterial-enhanced tumor-targeting bacterium From: Zheng et al. 2018, Nat Commun 9:1680 |
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Show notes:
Microbe of the episode: Maruca vitrata nucleopolyhedrovirus
Here's a paper I found that actually shows carbon dot nanomaterials enhancing bacterial nitrogen fixation
Journal Paper:
Zheng D-W, Chen Y, Li Z-H, Xu L, Li C-X, Li B, Fan J-X, Cheng S-X, Zhang X-Z. 2018. Optically-controlled bacterial metabolite for cancer therapy. Nat Commun 9:1680.
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Episode outline:
- Background: Using bacteria to treat cancer is very promising
- Some options just go all over and attack tumors selectively
- Some can be guided, like magnetotaxis
- Attach nanomaterials to target tumors, or engineer to produce anticancer compounds
- But can be hard to deliver adequate amounts
- Can't carry very much, and hard to get stable in situ production
- Hard to get enough electrons/energy to microbes in tumor environment
- What’s new: Now, scientists publishing in Nature Communications have created cyborg cancer-seeking bacteria that can absorb light energy to generate tumor-killing compounds!
- Methods: Took nonpathogenic strain of Escherichia coli, MG1655
- Already good at tumor targeting
- And has enzyme called nitrate reductase
- Adds electrons to nitrate ions, NO3-, can produce nitric oxide, NO
- Reactive compound, immune system produces to kill targets
- Making a lot locally can kill cancer
- But requires lots of electrons
- Bound bacteria to carbon-dot doped carbon nitride
- Nanomaterial semiconductor substance made of carbons and nitrogens in a matrix
- Carbon dots – carbon-based nanoparticles, absorb/interact with light
- So can absorb light and pass energy to bacteria by generating electron flow to enzymes
- Tested this combo with chemical test – reagent turns red if NO generated
- In light, combo generated a lot; bacteria or nanomaterial alone not as much
- Made enough NO in 15 min to kill cancer cells
- In dark, a lot less from combo
- Could measure current generated by nanomaterial, and rise in electron stores of bacteria
- And confirmed generation of NO from nitrate with 15-N nitrate
- Found similar effect could be achieved with CdS nanoparticles + bacteria
- Tested system in vitro – 3D-printed setup
- cancer cells in chamber surrounded by bacterial culture
- NO could diffuse through membrane between
- Could detect it in the cells with fluorescent detector compound
- Also observed cancer viability decreasing, up to 70% of cells killed in 24h
- Bacteria without the nanomaterial, or in dark, didn't kill
- Then tried in vivo – in mice with tumors
- Injected bacteria, detected fluorescence from them localized to tumor
- Negligible in liver and elsewhere
- But does it penetrate tumor tissue? Many synthetic carriers don't
- Sectioned samples to see how far in
- Actually most bacteria penetrated all the way in
- Bacteria cleared from mice within 3 weeks, and no side effects detected
- Antibiotics could help clear too
- And NO was produced – set up tumors to produce bioluminescence in response
- So how well does it work?
- Saw correlation between bacteria, NO, and tumor cell death
- Inhibited 70-80% of tumor growth in mice
- Nanomaterial and bacteria alone not very effective
- But together, produced NO that killed cells even at a distance
- Seemed to induce stronger immune response against cancer too
- Summary: Combined tumor-seeking bacteria with nanomaterial that absorbs light and uses it to generate electron flow, allowing bacteria to produce NO in tumor that kills it
- Applications and implications: Potentially useful system for cancer treatment
- If safe and effective in humans
- Electron flux is important for other things too
- Like nitrogen fixation; maybe help fertilize crops
- What do I think: Fascinating way to combine best of nanotechnology with microbiology
- Hope to see more in future
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