New treatment to heal osteoarthritis
Multiphoton microscopy: sphere-shaped molecules (blue) carry tissue-restoring growth factor and penetrate knee joint cartilage. [Brett Geiger and Jeff Wyckoff]
Researchers from MIT have designed a new material that can administer drugs directly to cartilage and could one day help to reverse osteoarthritis.
The material penetrates deep into this firm, connective tissue, delivering drugs that could potentially heal damaged tissue.
"This is a way to get directly to the cells that are experiencing damage, and introduce different kinds of therapeutics that might change their behaviour," says Paula Hammond, head of MIT's Department of Chemical Engineering, a member of MIT's Koch Institute for Integrative Cancer Research.
Rat studies revealed that delivering the drug, insulin-like growth factor 1 - IGF-1 - with this new material prevented cartilage breakdown more effectively than injecting the drug into the joint on its own.
Stunning multiphoton microscopy and reconstructions reveal that six days after treatment, the particles have penetrated through the cartilage of the knee joint (see top image).
Easing drug delivery
There are currently no disease-modifying drugs to treat osteoarthritis, a debilitating disease affecting the joints.
With this in mind, Hammond and colleagues designed sphere-shaped molecules to carry drugs all the way through the cartilage.
Their new nanocarriers contain positively-charged dendrimers, branching from a central core, that help it to bind to the negatively-charged cartilage and deliver the drug.
Crucially, the researchers were able to tune the surface charge of these nanocarriers by replacing some of the dendrimers' positive charges with a short, flexible polymer - PEG - that swings around to partially cover the remaining positive charges.
According to the researchers, when the nanocarriers are injected into a joint, they diffuse through the cartilage.
The flexible PEG chains then cover and uncover the positive dendrimer charges, so the molecule can briefly attach and then detach from cartilage, moving deeper and deeper into tissue.
"We found an optimal charge range so that the material can both bind the tissue and unbind for further diffusion, and not be so strong that it just gets stuck at the surface," says Hammond's colleague, Brett Geiger.
Once the particles reach the chondrocytes, the IGF-1 growth factor binds to receptors on the cell surfaces and stimulates the cells to start producing proteoglycans, the building blocks of cartilage and other connective tissues.
The IGF-1 also promotes cell growth and prevents cell death.
In animal studies, the researchers found that cartilage in injured joints treated with the new molecule-drug combination was far less damaged than cartilage in untreated joints or joints treated with IGF-1 alone. The joints also showed reductions in joint inflammation and bone spur formation.
The researchers believe the new material could be used to treat trauma- and age-related osteoarthritis.
They now plan to explore the possibility of delivering different types of drugs, such as other growth factors, drugs that block inflammatory cytokines, and nucleic acids such as DNA and RNA.
Research is published in Science Translational Medicine.