Swimming Particles - Future Drug Delivery Vehicles?

For my Ph.D. dissertation, I studied tiny metallic rods that propel themselves ("swim") through hydrogen peroxide.  You can read more about them in my previous post here.  When I tell people about these rods, the most common question I get is, "that's neat and all, but what can you use them for?"  It's a fair question.

My work was mostly focused on figuring out how the rods swim in the first place, which was fun in itself.  But there's some rather tasty icing on the cake: in addition to being interesting, it turns out that "nanomotors," the general term for microscopic swimmers such as the platinum-gold rods, may indeed have some important useful applications.

A rod-shaped "nanomotor" swims toward a piece of inert cargo (green), tugs it along for a short period (red), and releases it at a predetermined location before swimming away (green).

Above, we see that the rods can "tow" a piece of "cargo" (e.g. a tiny polystyrene sphere) from one pre-defined point to another (for more, see this previous post). Today we'll discuss one of the possibilities this raises, related to improving cancer treatment.

A Brief Introduction to Chemotherapy 

Chemotherapy (or "chemo") generally refers to the use of drugs to treat cancer.  Most chemo drugs are administered intravenously, entering the patient's bloodstream and attacking cells all over the body (including, but not limited to, the cancer cells - see note 1).  Thus, even when successful, chemotherapy often kills healthy cells, causing many of the serious side effects of chemo that you're probably familiar with (and may have experienced yourself).  It's kind of like setting off an atomic bomb inside the body; it destroys more than just the intended target.

Can we do better?

Targeted chemotherapy

There's a new type of cancer treatment known as targeted cancer therapy.  The idea is to make "smarter" drugs that target the attributes of cancer cells that make them cancerous in the first place.  As their name suggests, targeted cancer drugs need to be delivered to a specific location: directly to the tumor, rather than the whole body.  But drugs can't find cancer cells on their own.  To make targeted chemotherapy work, you typically need something to carry a drug directly to a cancer cell to kill it, but not harm the surrounding healthy cells in any way.  Instead of an atomic bomb, these drugs act like a sniper, only targeting the bad guys.

But how do you get the drug to the cancer cell?

Could Nanomotors Deliver Drugs?  

Enter Professor Joseph Wang, at the University of California, San Diego, and his research team (a one-time collaborator of ours).  They recently developed a different kind of swimmer from the ones I studied: they manufactured tiny, cylindrical tubes made of a bio-compatible (i.e., non-toxic) material coated with zinc.  They're about 20 micrometers long, about 1/5th as long as a human hair is wide.  Most importantly, these swimmers are powered not by peroxide (which is toxic to humans), but by acid: the zinc reacts with the hydrogen ions in the acid and turns them into hydrogen gas bubbles.  The bubbles are ejected from the tube, which acts kind of like a rocket: the recoil from the bubble release propels the swimmer forward, as illustrated below.

Schematic of zinc-powered nanomotors that use stomach acid as a fuel.  The chemical equation illustrates that solid zinc (on the motor surface) reacts with protons in the acid (H+), creating hydrogen bubbles (H2) which propel the swimmer forward.  Meanwhile, the zinc dissolves harmlessly into the acid (forming zinc ions, with a 2+ charge).

So, why would an acid-propelled swimmer be useful? Isn't acid harmful?

Well, the stomachs of many mammals, including ours, are highly acidic.  Acid, as you may recall, contains plentiful amounts of hydrogen ions, which are basically protons floating around in the solution.  So our stomachs are full of nanomotor fuel.

Professor Wang's research team built these swimmers and coated them with gold nanoparticles (tiny spheres of gold much smaller than the swimmers), which serve as a model "drug."  They administered the gold-laden nanomotors orally to live mice.  After 2 hours, the mice were, as we researchers politely put it, "sacrificed" (for science!) and their stomachs were examined.  Compared to mice that had received an oral dose of nanoparticles alone, the mice that received the nanoparticle-laden swimmers showed over three times as much retention of the gold in their stomach lining.

In other words, the nanomotors acted like delivery trucks, delivering the gold "drugs" into the mice's stomach linings!

The useful thing about these swimmers is that, like the platinum/gold rods I studied, they can carry payloads.  However, unlike the platinum-gold rods, they don't need hydrogen peroxide to move.  They just move based on the stomach acid that's already present!  Even better, the motors slowly dissolve in the stomach acid, leaving nothing toxic behind!

This is a step forward for the field of man-made micro-swimmers.  There are certainly still roadblocks to overcome, of course: for one thing, we need to show that this is viable in humans, and not just for delivering drugs into the stomach lining.  Remember, for targeted cancer treatment, we need to be able to guide these swimmers to a specific location - the swimmers here indiscriminately swam until they collided with the stomach lining.  We do have ways of guiding self-propelling particles, but guiding them to a tumor is still a ways away.

Still, this work shows that the idea of using nanomotors to deliver drugs is not simply a pie-in-the-sky idea, as some people believe.

NOTES!

1. If you're wondering, traditional chemotherapy drugs typically target cells that divide quickly.  Cancer cells divide quickly, which is why chemo drugs often work against them.  The problem is that there are many other cells in the body that also divide quickly but are completely healthy.  These cells are vulnerable to the chemo drugs.