Diabetic wounds, often resistant to conventional treatments, pose serious health risks to millions of people worldwide. For those with diabetes, immune cells known as macrophages, which are supposed to help, end up causing inflammation instead. This inflammation in turn harms other cells, making it harder for the wound to heal properly and quickly.

In a recent study published in the Proceedings of the National Academy of Sciences USA, researchers at the Icahn School of Medicine at Mount Sinai used lipid nanoparticles (LNPs) loaded with RNA encoding IL-4, a cell-to-cell signaling protein known as a cytokine, to target dysfunctional macrophages while simultaneously reducing inflammation and reactive oxygen species (ROS) in diabetic wounds.

ROS molecules are produced naturally in the body during various metabolic processes and play roles in cell signaling and immune responses. However, excessive ROS production can lead to oxidative stress, causing damage to cells, proteins, and DNA. This stress is associated with various diseases and conditions, including inflammation and aging.

"In preclinical models, we basically showed the therapy's ability to reprogram pro-inflammatory macrophages into reparative ones, leading to improved wound healing outcomes," says Yizhou Dong, PhD. "Dysfunctional macrophages drive diabetic non-healing wounds, but we can reprogram them to stop the damage and instead help the healing process. We aim to promote faster and more effective wound closure by reprogramming these cells and modulating the inflammatory environment."