How Ninja Particles Work

Human ninjas were renowned for swiftly and stealthily seeking and destroying their opponents. Ninja particles are like that, too, only microscopically.
Toshifumi Kitamura/AFP/Getty Images

Ninja were stealthy warriors in Japanese history who were often given the charge of infiltrating and assassinating enemies. Ninja particles do pretty much the same thing: attack and kill.

Created and named by researchers from IBM and Singapore's Institute of Bioengineering and Nanotechnology, these minuscule attackers may solve two issues that plague modern medicine: antibiotic-resistant bacteria and biofilms. On the first front, half of the hospitalized patients in the United States suffer from hospital-acquired infection with drug-resistant bacteria, according to some estimates, and the infections from these bacteria are becoming increasingly harder to treat [source: Liu]. Superbugs, like infection-causing methicillin-resistant Staphylococcus aureus and Escherichia coli, have evolved a resistance to traditional antibiotics. As a result, scientists and doctors are being forced to seek alternative treatment options to kill these bacteria. Second, the biofilms that form on the surfaces of medical devices also pose a huge problem. As these bacteria-ridden gunky substances coat catheters and other medical implants, the devices become a vehicle to carry bacteria into the body.


Enter the ninja particle. In classic ninja style, these tiny particles (1,000 times smaller than a grain of sand!) may one day be able to infiltrate the body, hunt down the offending bacterium and kill it in a way that leaves the microbe looking as if it's been attacked with a ninja star. Like its namesake, this particle is good at its job. It zeros in on its target and manages to leave other cells unharmed. The particles are equally skilled at wiping out biofilms that form on surfaces, making these petite ninjas forces to be reckoned with.

Keep reading to learn more about how these particles fought their way into the lab and what they can do for us.


What It Takes to Be a Ninja Particle

Looks like a bacterial cell with nothing to fear, right? Go to the next page to see what it looks like after a ninja particle gets to it.
Image courtesy IBM

When researcher Yi Yan Yang heard about the work chemist Jim Hedrick was doing at IBM on microelectronics, she immediately approached him about a collaboration, telling him his research advances could be put to better use in medicine. Since then, their partnership has resulted in the development of a very promising group of nanoparticles dubbed "ninja particles."

The human immune system inspired their creation. When a person gets sick, his or her body secretes antimicrobial peptides. These bacteria-fighting molecules seek out a microbe, latch onto it and kill it (that last part can happen in a few different ways). Hedrick and Yang set out to make a particle in the lab that would do the same thing.


The nanoparticle they created is made of a special type of polymer. Polymers are super long, chained molecules. Plastics, for example, are all polymers. The polymer nanoparticle that Hedrick and Yang developed has three parts that make it so adept at killing bacteria.

  1. The chains have a dopamine molecule hanging off it. Yup, we're talking about the same dopamine that helps to control the brain's reward and pleasure centers. Here, it's serving a purely functional purpose of helping to attach the polymer nanoparticle to its target.
  2. The long chains also contain a short chain of a different type of polymer, polyethylene glycol (or PEG). PEG has a lot of industrial and medicinal uses. In this case, it works to fight organism growth on surfaces, as a preventative measure to combat bacteria.
  3. Finally, the nanoparticles contain a positively charged portion that has antibacterial properties. This part helps to target the negatively charged bacteria in the body and kill them off once found.

With these three parts, ninja particles have been shown to be effective at killing methicillin-resistant Staphylococcus aureus (MRSA), E. coli and certain types of fungi [source: Yang]. In addition, the nanoparticles can be used to coat medical devices like catheters, which are notorious for growing bacteria-ridden biofilms. The coating prevents bacteria from forming on the surfaces, reducing the chance of infections in patients with these implanted devices.


Ninja Particles Target and Destroy

That's what the bacterial cell looks like after a ninja particle has set upon it: popped (or lysed).
Image courtesy IBM

So ninja particles are specially designed to target bacteria and kill them, but how? The first step is finding the offending bacterial cells in a sea of mammalian cells. This is where that key tenet of "opposites attract" takes hold. The surface of bacterial cells is more negatively charged than that of mammalian cells. In order to specifically be attracted to the bacterial cells, the ninja particles must have the opposite charge – positive. They garner this positive charge on their surface through a process called self-assembly. Each particle is made up many, many smaller strands of polymers. These polymers clump together, or self-assemble, to form little balls called micelles. Because of attractive interactions between different parts of the polymer chain, these micelles form naturally in water with the outside of the ball coated in a positive charge. And voila – the ball of positive charge is naturally attracted to the negatively charged microbe.

Once there, the ninja particle attaches itself to the bacterial cell. The positively charged portions of the particle that helped selectively find the bacterial cells also act as antibacterial agents, poking holes into the cell wall. This process, called membrane lysis, ruins the structure of the cell, causing the guts of the cell to start to ooze out, with no hope of recovery. This, in fact, is where the researchers came up with the name "ninja" for their particles. The kill method of perforating the cell wall with holes is similar to what might happen if the cell were attacked with a ninja star.


One of the best parts of this process is that bacteria are never given the chance to develop any resistance. Antibiotics work by selectively crippling certain parts of the cell's mechanism, keeping most of the structural features intact. The ninja particle method, in contrast, is very physically damaging to the cell, and the bacteria don't have the opportunity to potentially develop a resistance to the ninja particles [source: Nederberg et al].

The lifetime of the ninja particles can be fine-tuned so that they are able to kill the bacterial cells before being killed off themselves. Eventually, however, enzymes in the body start degrading the particles and they fall apart, with the resulting smaller bits getting excreted by the body [source: Hedrick].


Benefits of Using Ninja Particles to Treat Infections

Bacteriophages may pose another treatment option for doctors fighting bacterial infections.
Science Picture Co/Getty Images

With the move toward a post-antibiotic world, scientists have pushed to find alternative treatments for infection that don't involve antibiotics. Progress has been made with viruses called bacteriophages, which hijack the bacteria's inner machinery and cause it to burst like a balloon. Other work has been done with bacteria-made toxins (bacteriocins) to kill off infection-causing bacteria. The advances that most closely relate to ninja particles are therapies involving cationic or antimicrobial peptides. These molecules also can selectively target bacteria due to opposite attraction of charges on their surfaces. Their method of killing the bacterial cells is rooted in disruption of communication between cells [source: Borel]. This therapy, however, has been plagued with several issues: toxicity for healthy, nonbacterial cells (for example, mammalian cells may rupture and release their contents); short half-life in vivo (they don't last very long in the body) and high manufacturing costs [source: Nederberg et al].

Ninja particles solve a lot of these problems. They are compatible with blood, having minimal to no toxicity to red blood cells; are stable enough to remain effective in vivo; biodegrade easily and are orders of magnitude cheaper to make. Ninja particles aren't the only bacteria fighting particles out there. Researchers across the world have been making similar strides developing other small molecules with antimicrobial properties or creating nanoparticle-based approaches to drug delivery [sources: Zhu and Gao]. These particles join a growing community of nanoparticle-based therapies. Nanoparticles are used in medicinal applications such as medical imaging (like MRI) and in treatment of a wide range of diseases like cancer and AIDS.


Target Applications of Ninja Particles

Ninja particles have the potential to make a huge impact in our lives. Their demonstrated ability to seek out and kill antibiotic-resistant bacteria means we may one day see them in the form of an injectable drug. Researchers continue to gather data on the efficacy and toxicity (or lack of toxicity, actually) of these particles. Once they've completed their tests, pharmaceutical companies may step in to do human trials that monitor how these particles fight off bacterial infections inside the body.

Outside the body, we may start to see ninja particles used as a disinfectant and to stop biofilm formation. The bacteria that make up biofilms are very good at protecting themselves. Many sprays on the market have a hard time breaking through a biofilm's protective layers to disinfect surfaces. Ninja particles, on the other hand, are able to eradicate bacteria in these biofilms on contact, providing a great way to clean medical devices, or even food preparation surfaces.


These nanoparticles may find their way into our personal care products, too, essentially any place where we wouldn't want bacterial buildup. They may be used to coat contact lenses or placed as additives into things like mouthwash, deodorants and detergents. They can even be used in water purification systems. Bad bacteria are everywhere, and these ninja particles are poised to find and destroy them.

Lots More Information

Author's Note: How Ninja Particles Work

It's the best when something that has a cool name really lives up to its name. And ninja particles are about as awesome as their name implies. As I was writing this article, I loved imagining these particles stealthily zipping through the body, finding the bad bacteria guys and slitting them open. This research is so promising; I can't wait to find these particles on the market. The only part that makes me sad is that when they do one day make it into our personal care products or in our medications, that I won't be able to scroll through the ingredients and see "ninja particles" listed. Sadly, I think the FDA and other regulating organizations may require their actual chemical names. Too bad.

Related Articles

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  • Engler, Amanda C.; Wiradharma, Nikken; Ong, Zhan Yuin; Coady, Daniel J.; Hedrick, James; Yang, Yi Yan. "Emerging Trends in Macromolecular Antimicrobials to Fight Multi-Drug-Resistant Infections." Nano Today. Vol. 7. pp. 201-222. 2012.
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