Topical treatment with liposomes containing T4 endonuclease V protects human skin in vivo from ultraviolet-induced upregulation of interleukin-10 andtumor necrosis factor-alpha

Exposing human skin to ultraviolet radiation causes DNA damage, sunburn, im mune alterations, and eventually, skin cancer. We wished to determine wheth er liposomes containing a DNA repair enzyme could prevent any of the acute effects of irradiation when applied after ultraviolet exposure. Fifteen hum an patients with a prior history of skin cancer were exposed to two minimal erythema doses of ultraviolet radiation on their buttock skin. Liposomes c ontaining T4 endonuclease V or heat-inactivated enzyme were applied immedia tely and at 2, 4, and 5 h after ultraviolet irradiation. Transmission elect ron microscopy after anti-T4 endonuclease V-staining and immunogold labelin g on biopsies taken at 6 h after ultraviolet exposure revealed that the enz yme was present within cells in the skin. Immunohistochemical DNA damage st udies suggested a trend toward improved DNA repair at the active T4 endonuc lease V liposome-treated test sites. Although the active T4 endonuclease V liposomes did not significantly affect the ultraviolet-induced erythema res ponse and microscopic sunburn cell formation, they nearly completely preven ted ultraviolet-induced upregulation of interleukin-10 and tumor necrosis f actor-alpha RNA message and of interleukin-10 protein. These studies demons trate that liposomes can be used for topical intracellular delivery of smal l proteins to human skin and suggest that liposomes containing DNA repair e nzymes may provide a new avenue for photoprotection against some forms of u ltraviolet-induced skin damage.