New Method to Produce Ring-Opening Metathesis Polymers with Facile Degradability

A team of chemists at MIT has formulated a method to produce polymers that can disintegrate more readily in the body as well as in the environment.

A new type of polymer designed by MIT chemists incorporates a special monomer (yellow) that helps the polymers to break down more easily under certain conditions. (Image credit: Demin Liu)

A chemical reaction known as ring-opening metathesis polymerization (ROMP) is useful for developing innovative polymers for numerous uses such as high-performance resins, nanofabrication, and imaging agents or delivering drugs. But one shortcoming to this synthesis technique is that the resulting polymers do not naturally disintegrate in natural settings, such as within the human body.

The MIT study team has devised a way to enhance the degradability of those polymers by incorporating a new type of building block to the polymer’s backbone. This new building block, or monomer, develops chemical bonds that can be broken down by bases, weak acids, and ions like fluoride.

We believe that this is the first general way to produce ROMP polymers with facile degradability under biologically relevant conditions. The nice part is that it works using the standard ROMP workflow; you just need to sprinkle in the new monomer, making it very convenient.

Jeremiah Johnson, Study Senior Author and Associate Professor of Chemistry, MIT

It is possible to integrate this building block into polymers for a wide range of uses, including not just medical applications but also the synthesis of industrial polymers that would disintegrate more quickly after use, the scientists say.

The paper’s lead author, which has been published recently in Nature Chemistry, is MIT postdoc Peyton Shieh. Postdoc Hung VanThanh Nguyen is also one of the authors of the study.

Powerful Polymerization

Molecules known as norbornenes are the typical building blocks of ROMP-produced polymers. These molecules have a ring structure that can be effortlessly opened up and strung together to create polymers. Molecules such as imaging agents or drugs can be incorporated into norbornenes before the polymerization takes place.

Johnson’s lab has applied this synthesis method to develop polymers with many varied structures, such as bottlebrush polymers, linear polymers, and star-shaped polymers. These unique materials could be used for delivering several cancer drugs simultaneously, or for transporting imaging agents for magnetic resonance imaging (MRI) and other kinds of imaging.

It’s a very robust and powerful polymerization reaction. But one of the big downsides is that the backbone of the polymers produced entirely consists of carbon-carbon bonds, and as a result, the polymers are not readily degradable. That’s always been something we’ve kept in the backs of our minds when thinking about making polymers for the biomaterials space.

Jeremiah Johnson, Study Senior Author and Associate Professor of Chemistry, MIT

In order to avoid that problem, Johnson’s lab has concentrated on forming small polymers, of the order of about 10 nm in diameter, which could be eliminated from the body more easily compared to larger particles.

Other chemists have made attempts to render the polymers degradable by employing building blocks other than norbornenes; however, these building blocks do not polymerize as efficiently. It is also more challenging to attach drugs or other molecules to them, and they usually require harsh environments to break down.

We prefer to continue to use norbornene as the molecule that enables us to polymerize these complex monomers,” Johnson says. “The dream has been to identify another type of monomer and add it as a co-monomer into a polymerization that already uses norbornene.”

The scientists arrived at a probable solution through a research Shieh was performing on another project. He was seeking new ways to stimulate drug release from polymers, when he synthesized a ring-containing molecule that is analogous to norbornene but comprises an oxygen-silicon-oxygen bond.

The scientists learned that this kind of ring, known as silyl ether, can also be opened up and polymerized through the ROMP reaction, resulting in polymers with oxygen-silicon-oxygen bonds that break down without difficulty. Therefore, rather than using it for drug release, the scientists attempted to integrate it into the polymer backbone to make it degradable.

They discovered that by just incorporating the silyl-ether monomer in a 1:1 ratio with norbornene monomers, they could develop polymer structures similar to what they have earlier built, with the new monomer added fairly evenly throughout the backbone. Now, when exposed to a moderately acidic pH, of about 6.5, the polymer chain starts to fall apart.

It’s quite simple,” Johnson says. “It’s a monomer we can add to widely used polymers to make them degradable. But as simple as that is, examples of such an approach are surprisingly rare.”

Faster Breakdown

The MIT chemists found by testing mice that during the first week or two, the degradable polymers displayed the same distribution across the body as the original polymers. However, they started to disintegrate immediately after that.

At the end of six weeks, the concentrations of the new polymers in the body ranged between 3 and 10 times less than the concentrations of the original polymers, based on the precise chemical composition of the silyl-ether monomers used by the scientists.

The findings indicate that incorporating this monomer into polymers for imaging or drug delivery could help them get eliminated from the body more swiftly.

We are excited about the prospect of using this technology to precisely tune the breakdown of ROMP-based polymers in biological tissues, which we believe could be leveraged to control biodistribution, drug release kinetics, and many other features.

Jeremiah Johnson, Study Senior Author and Associate Professor of Chemistry, MIT

The scientists have also begun working on incorporating the new monomers into industrial resins, such as adhesives or plastics. They feel it would be economically viable to integrate these monomers into the production processes of industrial polymers, to render them more degradable. Moreover, they are partnering with Millipore-Sigma to market this class of monomers and make them accessible for research.

The study was supported by the National Institutes of Health, the American Cancer Society, and the National Science Foundation.


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