Engineered Carbon Nanomaterials for Prevention of UV-Induced Melanomagenesis
Abstract
Melanoma Research Program Focus Areas: Identify methods to decrease risk of melanoma development beyond traditional sunscreen and protective clothing Melanoma, while only 3% of all skin cancer cases, is highly dangerous with an estimated $3.3 billion in treatment costs and 6,850 deaths per year. Military personnel on active duty as well as Veterans have a higher risk of melanoma due to increased exposure to ultraviolet (UV) radiation from sunlight. A recent report suggests that the incidence of melanoma is increasing at a higher rate (40% vs 7%) among young military personnel than in the general population. U.S. Air Force personnel have the highest rates of melanoma, possibly due to intermittent exposure of high-intensity UV radiation. Melanoma is the most aggressive and deadly form of skin cancer and is notorious for developing diverse resistance mechanisms against drugs and radiation treatments. Exposure to UV radiation from sunlight is the most common, and also the most preventable, cause of melanoma. Dermatologists recommend sun avoidance and application of sunscreens to protect against these harmful effects of sunlight. However, avoiding the sun may be difficult in military environments. Traditional sunscreens only partially protect the skin from damaging UV rays and, unfortunately, have not been able to reduce the incidence of melanoma. Most chemicals used today to make sunscreens are unstable when exposed to sunlight, meaning that they are effective for a short time (only a few hours in the sun). These chemicals also generate highly reactive molecules called reactive oxygen species (ROS), which can themselves cause cancer. Another problem is that traditional sunscreens can harm marine life (kill coral reefs), and because of this, these chemicals are now banned in several states in the U.S. and other countries. More recent studies have raised questions about the safety of these sunscreens. Clinical studies from the Food and Drug Administration (FDA) show that the sunscreen chemicals can enter the bloodstream and remain in the body for days after a single use. Because of the unknown consequences of this, the FDA is proposing to remove all organic sunscreen chemicals from the FDA generally regarded as safe list. To circumvent these problems, we propose to design a new kind of sun-protective agent from engineered carbon nanomaterials (ECNs). ECNs absorb all parts of the UV spectrum without producing any ROS. Furthermore, they can neutralize ROS produced elsewhere in the skin by UV light. ECNs are safer than traditional sunscreens, as they cannot penetrate skin to enter the bloodstream. Our first objective is to design ECN-containing formulations, determine their UV absorption properties, and assess their ability to prevent and destroy ROS in human skin tissue. Our second objective is to demonstrate that ECN can prevent melanoma formation after UV exposure in a mouse model. We will also look at biological mechanisms to determine if ECNs can protect the skin from different pathways of UV-induced melanoma initiation. The information obtained from this study will provide data necessary to design future human clinical trials.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211041
Entities
People
- Vijay Krishna
Organizations
- Cleveland Clinic
- United States Army