Acceleration of wound healing by alpha-gal nanoparticles interacting with the natural anti-Gal antibody

Abstract

Application of alpha-gal nanoparticles to wounds and burns induces accelerated healing by harnessing the natural anti-Gal antibody which constitutes ~1% of human immunoglobulins. alpha-gal nanoparticles present multiple alpha-gal epitopes (Galalpha1-3Galbeta1-4GlcNAc-R), the carbohydrate ligand of anti-Gal. Studied alpha-gal nanoparticles were comprised of glycolipids with alpha-gal epitopes, phospholipids, and cholesterol. Binding of anti-Gal to alpha-gal nanoparticles in wounds activates the complement cascade, resulting in formation of chemotactic complement cleavage peptides that induce rapid recruitment of many macrophages. The Fc/Fcgamma receptors interaction between anti-Gal coating alpha-gal nanoparticles and the recruited macrophages activates macrophages to produce cytokines/growth factors that promote wound healing and recruit stem cells. Studies of wound healing by alpha-gal nanoparticles were feasible in alpha1,3galactosyltransferase knockout mice and pigs. In contrast to other nonprimate mammals, these mice and pigs lack the alpha-gal epitope, and thus they are not immunotolerant to it and produce anti-Gal. Treatment of skin wounds and burns with alpha-gal nanoparticles resulted in 40-60% decrease in healing time in comparison with control wounds treated with saline. This accelerated healing is associated with increased recruitment of macrophages and extensive angiogenesis in wounds, faster regrowth of epidermis, and regeneration of the dermis. The accelerated healing further decreases and may completely eliminate fibrosis and scar formation in wounds. Since healing of internal injuries is mediated by mechanisms similar to those in external wound healing, it is suggested that alpha-gal nanoparticles treatment may also improve regeneration and restoration of biological function following internal injuries such as surgical incisions, myocardial ischemia following infarction, and nerve injuries.