Will Nanotechnology Save Us From Drug-Resistant Bacteria?

staphThe future: injecting tiny nanoparticles into our bodies to fight the superbugs against which our immune systems are powerless. How could that ever go wrong? Via Technology Review:

Researchers at IBM are designing nanoparticles that kill bacteria by poking holes in them. The scientists hope that the microbes are less likely to develop resistance to this type of drug, which means it could be used to combat the emerging problem of antibiotic resistance.

IBM’s labs aren’t equipped for biological tests, so the researchers collaborated with Yi Yan Yang at the Singapore Institute of Bioengineering and Nanotechnology to test the nanoparticles. They found that the nanoparticles could burst open and kill gram-positive bacteria, a large class of microbes that includes drug-resistant staph. The nanoparticles also killed fungi.

The IBM researchers believe the drug could be injected intravenously to treat people with life-threatening infections. Or it could be made into a gel that could be applied to wounds to treat or prevent infection.

However, other drugs that work by this membrane-piercing mechanism have not been very successful so far. Those that have shown early promise on the lab bench either were toxic to animal cells or simply didn’t work in the complex environment of the human body.

More tests will be needed to say definitively whether the nanoparticles are safe and will work in people. Initial tests of the IBM particles with human blood cells and in live mice have been promising.

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  • Anonymous

    No, it won’t. Pasteur was wrong. Killing the bacteria will not reverse the disease state.

  • JoiquimCouteau

    No, it won’t. Pasteur was wrong. Killing the bacteria will not reverse the disease state.

    • http://hormeticminds.blogspot.com/ Chaorder Gradient

      Pasteur retracted his germ theory before he died in favor of the other major theory that bacteria/viruses do not cause the diseases. the alternative theory claimed the “invaders” arose from the disease and not the other way around.

      • JoiquimCouteau

        Aye, and Pasteur had plagiarized his germ theory from Bechamp in the first place, but was an oaf and did not understand it fully.

  • http://hormeticminds.blogspot.com/ Chaorder Gradient

    Pasteur retracted his germ theory before he died in favor of the other major theory that bacteria/viruses do not cause the diseases. the alternative theory claimed the “invaders” arose from the disease and not the other way around.

  • http://hormeticminds.blogspot.com/ Chaorder Gradient

    On another note, how the hell do you make sure these nanoparticles that pierce membranes will “chose” to destroy the membranes of bacteria rather than human cells…

  • Anonymous

    Aye, and Pasteur had plagiarized his germ theory from Bechamp in the first place, but was an oaf and did not understand it fully.

  • http://hormeticminds.blogspot.com/ Chaorder Gradient

    On another note, how the hell do you make sure these nanoparticles that pierce membranes will “chose” to destroy the membranes of bacteria rather than human cells…

  • Anonymous

    From the paper,

    “We hypothesize that the cationic micelles can interact easily with the negatively charged cell wall by means of an electrostatic interaction, and the steric hindrance imposed by the mass of micelles in the cell wall and the hydrogen-binding/electrostatic interaction between the cationic micelle and the cell wall may inhibit cell wall synthesis38 and/or damage the cell wall, resulting in cell lysis. In addition, the micelles may easily permeate the cytoplasmic membrane of the organisms due to the relatively large volume of the micelles9, destabilizing the membrane as a result of electroporation and/or the sinking raft model21, leading to cell death. To further study the interactions between the microbes and the polycarbonate micelles, we plan to incorporate a metal element into the polycarbonate in the future, which would allow clear visualization of the polymer nanoparticles within the microbes at different time points by means of TEM.

    Haemolysis is a major harmful side effect of many cationic antimicrobial peptides and polymers. The haemolysis of mouse red blood cells was evaluated after incubation with polymers 1 and 3 at various concentrations. Although the polymers disrupt microbial walls/membranes efficiently (Fig. 3), they do not damage red blood cell membranes. Therefore, little haemolysis was observed, even at a concentration of 500 µg ml−1 (81 and 54 µM for polymers 1 and 3, respectively) (Supplementary Fig. S12), a concentration well above their respective MICs. The surfaces of Gram-positive bacteria and fungi are much more negatively charged than those of red blood cells39. Therefore, the electrostatic interaction between the surfaces of the bacteria/fungi and the cationic micelles is much stronger than that between the surfaces of the red blood cells and the cationic micelles, leading to excellent antimicrobial activity, but insignificant haemolytic activity.

    To demonstrate the potential of the antimicrobial polymers in in vivo applications, we used polymer 1 as an example and evaluated its in vivo toxicity level. The LD50 of polymer 1 (the lethal dose at which half the mice were killed) was determined to be 31.5 mg kg−1 via intravenous injection. We also investigated the acute toxicity that the polymer might cause to major organs (the liver and kidney) and the balance of electrolytes in the blood by analysing levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea nitrogen, and sodium and potassium ions in blood samples obtained from treated mice 48 h post-injection. The levels of the functional parameters of the liver and kidney and the concentrations of potassium and sodium ions (Table 1) were unchanged 48 h after intravenous injection of polymer 1 at a concentration well above the MIC of the polymer (dose, 12 mg kg−1; estimated concentration in the blood, 39 µM, assuming that the blood volume of the mouse is ~1 ml). This indicates that the micelles do not cause significant acute damage to liver and kidney functions, nor do they interfere with the electrolyte balance in the blood. Importantly, these parameters remain unchanged, even at 14 days post-injection. In addition, no mouse treated with the polymer died, and no colour change was observed in the serum samples and urine of the mice treated with the polymer when compared with the control group. These findings demonstrate that the polymer did not induce significant toxicity to the mice during the period of testing. Nonetheless, preclinical studies should be conducted in the future to further evaluate potential long-term toxicity of the antimicrobial polymers before clinical applications.”

    It seems that the problem is that it indiscriminately kills bacteria based on electrical gradients, rather then that it kills eukaryotic cells. Although it might still do both, the toxicity testing they did was pretty basic

  • http://profiles.google.com/cllacar Carlo Llacar

    is there a kill switch on these nanoparticles, before they mistakenly overtake our bodies

  • http://flavors.me/carlo_llacar O_U

    is there a kill switch on these nanoparticles, before they mistakenly overtake our bodies

    • quartz99

      Most likely they’ll have a very very short battery life, just long enough to get in and do what they’re there to do (I don’t now how long that would be. An hour maybe? Less than a day, surely). The question then is, how do you remove them from the body?

      • JoiquimCouteau

        They’re not robots, ‘nanoparticle’ just means a large chemical compound. They aren’t powered in any way, they’re proteins that kill bacteria.

      • JoiquimCouteau

        They’re not robots, ‘nanoparticle’ just means a large chemical compound. They aren’t powered in any way, they’re proteins that kill bacteria.

  • http://voxmagi-necessarywords.blogspot.com/ VoxMagi

    RULE US FROM WITHIN, MY TINY OVERLORDS!!!

  • http://voxmagi-necessarywords.blogspot.com/ VoxMagi

    RULE US FROM WITHIN, MY TINY OVERLORDS!!!

  • Anonymous

    Apparently, electrical gradients. The problem isn’t killing eukaryotic cells but rather indiscriminately killing bacteria and possibly mitochondria. From the paper,

    “We hypothesize that the cationic micelles can interact easily with the negatively charged cell wall by means of an electrostatic interaction, and the steric hindrance imposed by the mass of micelles in the cell wall and the hydrogen-binding/electrostatic interaction between the cationic micelle and the cell wall may inhibit cell wall synthesis38 and/or damage the cell wall, resulting in cell lysis. In addition, the micelles may easily permeate the cytoplasmic membrane of the organisms due to the relatively large volume of the micelles9, destabilizing the membrane as a result of electroporation and/or the sinking raft model21, leading to cell death. To further study the interactions between the microbes and the polycarbonate micelles, we plan to incorporate a metal element into the polycarbonate in the future, which would allow clear visualization of the polymer nanoparticles within the microbes at different time points by means of TEM.

    Haemolysis is a major harmful side effect of many cationic antimicrobial peptides and polymers. The haemolysis of mouse red blood cells was evaluated after incubation with polymers 1 and 3 at various concentrations. Although the polymers disrupt microbial walls/membranes efficiently (Fig. 3), they do not damage red blood cell membranes. Therefore, little haemolysis was observed, even at a concentration of 500 µg ml−1 (81 and 54 µM for polymers 1 and 3, respectively) (Supplementary Fig. S12), a concentration well above their respective MICs. The surfaces of Gram-positive bacteria and fungi are much more negatively charged than those of red blood cells39. Therefore, the electrostatic interaction between the surfaces of the bacteria/fungi and the cationic micelles is much stronger than that between the surfaces of the red blood cells and the cationic micelles, leading to excellent antimicrobial activity, but insignificant haemolytic activity.

    To demonstrate the potential of the antimicrobial polymers in in vivo applications, we used polymer 1 as an example and evaluated its in vivo toxicity level. The LD50 of polymer 1 (the lethal dose at which half the mice were killed) was determined to be 31.5 mg kg−1 via intravenous injection. We also investigated the acute toxicity that the polymer might cause to major organs (the liver and kidney) and the balance of electrolytes in the blood by analysing levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea nitrogen, and sodium and potassium ions in blood samples obtained from treated mice 48 h post-injection. The levels of the functional parameters of the liver and kidney and the concentrations of potassium and sodium ions (Table 1) were unchanged 48 h after intravenous injection of polymer 1 at a concentration well above the MIC of the polymer (dose, 12 mg kg−1; estimated concentration in the blood, 39 µM, assuming that the blood volume of the mouse is ~1 ml). This indicates that the micelles do not cause significant acute damage to liver and kidney functions, nor do they interfere with the electrolyte balance in the blood. Importantly, these parameters remain unchanged, even at 14 days post-injection. In addition, no mouse treated with the polymer died, and no colour change was observed in the serum samples and urine of the mice treated with the polymer when compared with the control group. These findings demonstrate that the polymer did not induce significant toxicity to the mice during the period of testing. Nonetheless, preclinical studies should be conducted in the future to further evaluate potential long-term toxicity of the antimicrobial polymers before clinical applications.”

  • Anonymous

    Beware the Replicators!

  • GoodDoktorBad

    Beware the Replicators!

  • Brocksbiz

    Wow….

  • Brocksbiz

    Wow….

  • Hadrian999

    what could possibly go wrong

  • Hadrian999

    what could possibly go wrong

  • whatever

    the internet, a technology any uneducated person can use to rant against scientific progress,how could that ever go wrong?

  • whatever

    the internet, a technology any uneducated person can use to rant against scientific progress,how could that ever go wrong?

    • Hadrian999

      considering modern medical science can’t make sure nasal spray is safe i question they’re ability to make safe microscopic stabby-bots

  • Hadrian999

    considering modern medical science can’t make sure nasal spray is safe i question they’re ability to make safe microscopic stabby-bots

  • Apis

    Hey I’d like to thank my disinfo peeps for posting articles on superbugs. I’m actually researching superbugs and it’s very helpful to see this information posted on my favorite site!

  • Apis

    Hey I’d like to thank my disinfo peeps for posting articles on superbugs. I’m actually researching superbugs and it’s very helpful to see this information posted on my favorite site!

  • Apis

    Hey I’d like to thank my disinfo peeps for posting articles on superbugs. I’m actually researching superbugs and it’s very helpful to see this information posted on my favorite site!

  • Anonymous

    Most likely they’ll have a very very short battery life, just long enough to get in and do what they’re there to do (I don’t now how long that would be. An hour maybe? Less than a day, surely). The question then is, how do you remove them from the body?

  • Anonymous

    They’re not robots, ‘nanoparticle’ just means a large chemical compound. They aren’t powered in any way, they’re proteins that kill bacteria.

  • Anonymous

    They’re not robots, ‘nanoparticle’ just means a large chemical compound. They aren’t powered in any way, they’re proteins that kill bacteria.

  • http://www.facebook.com/vincentbill Bill Vincent

    I, for one, welcome our new nanotech overlords.

  • http://www.facebook.com/vincentbill Bill Vincent

    I, for one, welcome our new nanotech overlords.

  • Sumuduhimesha
21
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