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These biodegradable drug nanocarriers adhere to the extracellular matrix of cartilage, improving drug efficacy in joints during surgery or arthroscopy for those with osteoarthritis. Osteoarthritis (OA) is a disease characterized by the degeneration of cartilage in any joints in the body. This disease affects approximately 27 million Americans and has no cure. Available intra-articular medications for osteoarthritis are largely unsuccessful because they clear from the joint before the therapy can take full effect.
Researchers at the University of Florida have developed a site-specific drug delivery platform that binds directly to cartilage tissue after direct application. Within this therapy lies a strategic solution for prolonging drug retention in the targeted cartilage, enhancing the efficacy of osteoarthritis drug candidates.
Drug delivery nanoparticles improve retention and targeting of osteoarthritis therapeutics
This drug delivery platform comprises biodegradable drug nanocarriers functionalized to bind to the extracellular matrix of cartilage or adhere to cartilage surfaces when directly applied. Because they adhere to the cartilage with the help of a polymer sealant, the nanoparticles are sealed in place with the drug, which enables sustained drug localization at target tissue sites. Researchers envision surgeons would paint or spray these drug delivery nanoparticles into joints during surgery or arthroscopy to minimize or eliminate the need for intra-articular drug injections. Ultimately, this site-specific drug delivery platform could improve the retention of drugs in the cartilage at effective concentrations. It can also minimize off-target effects and lower drug dosing requirements.
These nanoparticles enable the delivery of nucleic acids or drugs to immunosuppressed natural killer (NK) cells to restore their cytotoxic functions in tumor microenvironments. Globally, cancer causes one of every six deaths, with the number of new cases expected to rise to 23.6 million per year by 2030. An important part of the human immune system, NK cells have the capacity to rapidly identify and eliminate cancerous cells in the body. However, solid tumors often develop an immunosuppressive microenvironment that inhibits the infiltration and cytotoxic functions of these NK cells. Other available technologies can deliver nucleic acids to the NK cells in order to reactivate their cytotoxic abilities, but they require using viral vectors as the method of delivery. NK cells are notoriously difficult to genetically manipulate, and even viral vectors and remain inefficient.
Researchers at the University of Florida have developed manganese dioxide nanoparticles that serve as a non-viral drug delivery system for NK cells in order to restore their cancer-killing functions. These nanoparticles transfect the NK cells without any additional physical assistance, such as magnetic stimulation or electroporation.
Intracellular drug delivery system that uses nanoparticles to transfect natural killer cells
The nanoparticles are composed of manganese dioxide, which catalyzes the breakdown of hydrogen peroxide to form oxygen and water. This serves to protect NK cells from oxidative stress generated in the hypoxic tumor microenvironment. Additionally, these nanoparticles facilitate the delivery of reactivating drugs and nucleic acids, specifically DNA and RNA molecules, to immunosuppressed natural killer cells to restore their anticancer immune functions. A cationic surface polymer can form a complex with DNA and RNA to deliver them into NK cells. The NK cells readily uptake these molecules and other medicinal compounds. For example, a nanoparticle complex with a silencing RNA will silence the transforming growth factor beta (TGF-β) cytokine, which cancer cells produce to inhibit NK cells. This combination of oxidative stress modification and TGF-β silencing promotes the reactivation of NK cells within a tumor microenvironment, inducing an immunotherapeutic response.
These nanoparticles break down the reactive oxygen species (ROS) generated during joint trauma and inflammation, thereby mitigating oxidative stress in order to treat or prevent osteoarthritis (OA) as well as other inflammatory diseases. Oxidative stress plays a central role in the initiation and propagation of osteoarthritis. The global market for osteoarthritis treatment is projected to exceed $11 billion by 2025. Osteoarthritis is a painful degenerative joint disease that involves the erosion of joint cartilage and underlying bone through mechanical strain and low-grade inflammatory processes largely resulting from oxidative stress. Treatments for osteoarthritis include surgery, regular hyaluronan injections, and long-term pain medication use; however, these treatments are expensive, are often ineffective, and can also produce unwanted side effects. Small molecule antioxidants have poor bioavailability and stability and are rapidly cleared from the joint after injection. Available treatments do not effectively address the oxidative stress on tissues that leads to joint degradation and inflammation.
Researchers at the University of Florida have developed bioactive manganese dioxide nanoparticles that localize to cartilage tissue and scavenge hydrogen peroxide and other reactive oxygen species, thereby reducing oxidative stress, protecting the cartilage from deterioration, and decreasing the joint pain and inflammation associated with osteoarthritis.
Bioreactive nanoparticles that reduce oxidative stress to protect joints and treat pain and inflammation in osteoarthritis
These bioactive nanoparticles neutralize upregulated reactive oxygen species (ROS) to relieve the oxidative stress in joint tissues that lead to osteoarthritis. The nanoparticles engineered with properties that enable colloidal stability in biological fluids, including synovial fluid in joints, and enable uptake into cartilage. Upon injection into an arthritic joint, the nanoparticles penetrate into the joint’s cartilage and catalyze the breakdown of hydrogen peroxide and other reactive oxygen species, relieving oxidative stress and inflammation. The nanoparticles remain in the tissue for a significant post-injection period, providing prolonged treatment for the inflammation.
