LAUSR

Pathogenic bacteria induced subcutaneous infections pose serious threats to global public health. Recently, photodynamic therapy (PDT) has been proposed as a non-invasive approach for anti-microbial treatment, without the risk to induce drug-resistance. However, due to the hypoxic environment of most anaerobiont infected site, the therapeutic efficacy of oxygen consuming PDT has been limited. Herein, w e report a transdermal delivery system to allow effective delivery of photosensitizers into infected skins for PDT treatment of skin infections by bacteria. Considering the over-production of hydrogen peroxide (H2 O2 ) in the abscess area, catalase (CAT), an enzyme that triggers H2 O2 decomposition to generate O2 , is conjugated with chlorine e6 (Ce6) to form a photosensitizer conjugate (Ce6-CAT) as an enhanced PDT agent against S. aureus. After screening a series of fluorinated low molecular weight polyethylenimine (F-PEI) with different fluorination degrees, w e identified the optimized F-PEI formulation with the best transdermal delivery ability system. Upon mixing, the formed Ce6-CAT@F-PEI nanocomplex showed effective transdermal penetration after being applied onto the skin surface. With light exposure of the infected skin, w e observed highly effective in vivo anti-bacterial PDT therapeutic effect with Ce6-CAT@F-PEI. O ur work proposes a transdermal PDT therapeutic nanomedicine particularly promising for anti-bacterial treatment of skin infections. This article is protected by copyright. All rights reserved.