Development of nanoparticles loaded with D-mannose for topical treatment to alleviate skin aging via rescuing SIRT1 from degradation.

Skin aging is a complicated biological process, greatly interrupting skin physical function and increasing the risk of aging-associated skin diseases, therefore, drugs or treatment to delay or even reverse this process is in urgent need. D-mannose, a monosaccharide metabolite existing in human body and nature, has been demonstrated as a protential beneficial supplementation in clinical practice. However, whether D-mannose could alleviate skin aging remains unclear. Based on our previous study, we initially investigated the effect of topical supplementation of D-mannose on skin aging and found that it markedly rescued the senescent phenotype and recovered extracellular matrix disposition in the aging skin mice model. Considering that exogenous D-mannose predominantly eneters in lysosomes and subsequently exerts its biological functions, we therefore constructed a nanomaterial-loaded-D-mannose (MSN-B-Man) which could deliver D-mannose to lysosomes precisely. Furthermore, we observed prolonged skin retention of D-mannose and stronger anti-senescent effect upon topical application of MSN-B-Man compared with D-mannose alone. Mechanistically, D-mannose, cargo of MSN-B-Man, could physically bound with SIRT1 to prevent SIRT1 degradation in skin fibroblast during senescence, thus activating autophagy and further suppressing skin aging. Therefore, our present results first time unveil a novel protective role and underlying mechanisms of D-mannose during the skin aging course, highlighting the potential application of topical MSN-B-Man administration in alleviating skin aging and skin aging-related diseases.