This is one in a series presenting news on technology and innovation, made possible with generous support from the Lemelson Foundation.
Cancer drugs need to be powerfully toxic to kill tumor cells. But they also can kill healthy cells, sometimes with brutal side effects. Now, scientists have designed a way to seal cancer drugs inside tiny capsules so the drugs won’t harm the healthy cells while traveling through the bloodstream. They hold that medicine securely until they reach a tumor and a remote control “switch” finally triggers the drug’s release.
Smaller than bacteria, the capsules are called nanoparticles because their size is measured in nanometers. (A nanometer is equal to one billionth of a meter, or 3 billionths of a foot.) A magnetic field is the invisible force generated by a magnet.
Researchers use a magnetic field to work as that remote control switch. Focusing that field on the cancer site ensures that the medicine is released only where it’s needed.
“The drug is not toxic while it’s inside the particle,” explains Carlos Rinaldi. He’s a biomedical engineer at the University of Florida in Gainesville. He led the team that designed the remotely activated particles.
The nanoparticles don’t seek tumors out. They do, however, tend to collect at tumor sites. And here’s how. Tumors tend to grow so fast that the blood vessels inside them can’t keep up. This causes holes to form in the blood vessels. For a nano-package carrying the medicine, those leaky spots become a doorway from the bloodstream into the tumor. The nanoparticles slip in through those leaks,then accumulate in the tumor.
Nanoparticles also can pile up in unwanted places. One such unhelpful collection point is the liver. This organ acts as a filter, snagging poisons out of the blood. It will also net some nanoparticles. Those caught in the liver could damage that organ if they shed too much of an anti-cancer drug.
For many years, researchers have studied how to make nanoparticles that won’t drop their drug cargo at such unwanted sites. Sometimes they relied on a chemical trait of the tumor — or the enzymes it produces — to unlock the particles. But not all cancers have the same chemistry. So the medicine might still leak out to poison cells outside the tumor. The new innovation by Rinaldi’s team is the creation of a a nanoparticle that won’t release its medicine anywhere until it gets very warm. And that warming occurs when the particle is exposed to a magnetic field.
The team published its findings January 9 in ACS Applied Polymer Materials.
The nano-package contains two types of particles inside a thin wall, or membrane. Picture something like a gumball machine, with two types of gumballs inside. The first gumball is a nanoparticle made of iron oxide. This metal responds to magnetic fields. Think of a paper clip that jumps to meet a refrigerator magnet. These particles also react when zapped with a certain type of magnetic field. Here, instead of jumping, they warm up.
The second type of gumball is a polymer (PAHL-ih-mur). This type of molecule is made from long chains of the same building blocks. The researchers figured out how to lock this polymer onto a molecule of a cancer-fighting drug. They’re linked using a type of chemical bond that breaks when it gets hot.
Next, Rinaldi’s team wrapped each gumball pair in a water-friendly jacket. This allows the nanoparticles to travel through the blood, which is water-based. The coating also acts as a disguise. It hides the nanoparticles from the body’s immune system. Each two-“gumball” package measures about 100 nanometers (0.0000039 inch) across. For perspective, a red blood cell is about 70 times that size.
When exposed to a specific type of magnetic field, the iron-oxide “gumball” in each package heats up. That breaks the bonds holding the medicine inside and sends it flooding out into the tumor.
For this new treatment, Rinaldi and his colleagues use a special machine that restricts where the field contacts the body. They can target that field to the tumor site. Nanoparticles in the liver or any other healthy organ won’t be exposed to the magnetic field. And that means any particles in them won’t release the drug.
Because the drug will be released only at the tumor, patients now can take higher doses of toxic cancer drugs without poisoning healthy parts of the body.
Not yet ready for the clinic
Chemotherapy using the new particles is still a ways off. The current work is a “proof of principle,” Rinaldi says. That means that he and his team have not yet tested the system on living cells, much less in animals. In fact, they still haven’t packed their particles with real drugs yet. In place of a drug, the researchers attached a glowing fluorescent (Flor-ESS-ent) molecule to the iron-oxide “gumballs.” That made it easy to track where and when the chemical was released in response to the magnetic field.
It would be “a major advance,” he says, "if they can really guarantee that these particles do not release [a] drug without [a] magnetic field,” says Amit Joshi. He’s a biomedical engineer at the Medical College of Wisconsin in Milwaukee. He works on nanoparticles but was not involved in this study. However, he cautions, without animal testing, “we don’t know how stable it is.” Even if nanoparticles work well in the lab, there is no guarantee they would work equally well inside the body.
The new nanoparticles do have features that make them look promising for medicine, Joshi says. The U.S. Food and Drug Administration has already approved iron-oxide nanoparticles for use in the body, he points out. And the magnetic fields used to trigger drug release by the new particles can reach tumors deep inside the body without surgery, he explains. That should make their use easier on patients.
“This is really, I would argue, for us, a small step,” Rinaldi says. “There’s a lot of things we don’t understand very well.” But every small step brings the technology closer to real-world use. In the end, he concludes: “It’s an exciting field with a lot of potential applications.”
application A particular use or function of something.
bacteria (singular: bacterium) Single-celled organisms. These dwell nearly everywhere on Earth, from the bottom of the sea to inside other living organisms (such as plants and animals). Bacteria are one of the three domains of life on Earth.
biomedical engineer An expert who uses science and math to find solutions to problems in biology and medicine; for example, they might create medical devices such as artificial knees.
blood vessel A tubular structure that carries blood through the tissues and organs.
bond (in chemistry) A semi-permanent attachment between atoms — or groups of atoms — in a molecule. It’s formed by an attractive force between the participating atoms. Once bonded, the atoms will work as a unit. To separate the component atoms, energy must be supplied to the molecule as heat or some other type of radiation.
cancer Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall.
chemical A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.
chemistry (about compounds) Chemistry also is used as a term to refer to the recipe of a compound, the way it’s produced or some of its properties. People who work in this field are known as chemists.
chemotherapy A chemical treatment that’s most often used to kill cancer cells in the body. Chemotherapy can have many unpleasant side effects as it kills not only cancer cells but many healthy cells as well.
colleague Someone who works with another; a co-worker or team member.
enzymes Molecules made by living things to speed up chemical reactions.
field (in physics) A region in space where certain physical effects operate, such as magnetism (created by a magnetic field), gravity (by a gravitational field), mass (by a Higgs field) or electricity (by an electrical field).
filter (in chemistry and environmental science) A device or system that allows some materials to pass through but not others, based on their size or some other feature. (in physics) A screen, plate or layer of a substance that absorbs light or other radiation or selectively prevents the transmission of some of its components.
fluorescent (v. fluoresce) Adjective for something that is capable of absorbing and reemitting light. That reemitted light is known as fluorescence.
Food and Drug Administration (or FDA) A part of the U.S. Department of Health and Human Services, FDA is charged with overseeing the safety of many products. For instance, it is responsible for making sure drugs are properly labeled, safe and effective; that cosmetics and food supplements are safe and properly labeled; and that tobacco products are regulated.
force Some outside influence that can change the motion of a body, hold bodies close to one another, or produce motion or stress in a stationary body.
immune system The collection of cells and their responses that help the body fight off infections and deal with foreign substances that may provoke allergies.
innovation (v. to innovate; adj. innovative) An adaptation or improvement to an existing idea, process or product that is new, clever, more effective or more practical.
liver An organ of the body of animals with backbones that performs a number of important functions. It can store fat and sugar as energy, break down harmful substances for excretion by the body, and secrete bile, a greenish fluid released into the gut, where it helps digest fats and neutralize acids.
magnet A material that usually contains iron and whose atoms are arranged so they attract certain metals.
magnetic field An area of influence created by certain materials, called magnets, or by the movement of electric charges.
major (in education) A subject that a student chooses as his or her area of focus in college, such as: chemistry, English literature, German, journalism, pre-medicine, electrical engineering or elementary education.
membrane A barrier which blocks the passage (or flow through) of some materials depending on their size or other features. Membranes are an integral part of filtration systems. Many serve that same function as the outer covering of cells or organs of a body.
metal Something that conducts electricity well, tends to be shiny (reflective) and malleable (meaning it can be reshaped with heat and not too much force or pressure).
molecule An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).
nanoparticle A small particle with dimensions measured in billionths of a meter.
organ (in biology) Various parts of an organism that perform one or more particular functions. For instance, an ovary is an organ that makes eggs, the brain is an organ that makes sense of nerve signals and a plant’s roots are organs that take in nutrients and moisture.
oxide A compound made by combining one or more elements with oxygen. Rust is an oxide; so is water.
particle A minute amount of something.
polymer A substance made from long chains of repeating groups of atoms. Manufactured polymers include nylon, polyvinyl chloride (better known as PVC) and many types of plastics. Natural polymers include rubber, silk and cellulose (found in plants and used to make paper, for example).
red blood cell Colored red by hemoglobin, these cells move oxygen from the lungs to all tissues of the body. Red blood cells are too small to be seen by the unaided eye.
side effects Unintended problems or harm caused by a procedure or treatment.
technology The application of scientific knowledge for practical purposes, especially in industry — or the devices, processes and systems that result from those efforts.
toxic Poisonous or able to harm or kill cells, tissues or whole organisms. The measure of risk posed by such a poison is its toxicity.
trait A characteristic feature of something.
tumor A mass of cells characterized by atypical and often uncontrolled growth. Benign tumors will not spread; they just grow and cause problems if they press against or tighten around healthy tissue. Malignant tumors will ultimately shed cells that can seed the body with new tumors. Malignant tumors are also known as cancers.
Journal: E.G. Fuller et al. Externally triggered heat and drug release from magnetically ontrolled nanocarriers. ACS Applied Polymer Materials. Vol. 1, February 8, 2019, p. 211. doi: 10.1021/acsapm.8b00100.