Transdermal Delivery of Photosensitizer-Catalase Conjugate by Fluorinated Polyethylenimine for Enhanced Topical Photodynamic Therapy of Bacterial Infections.

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 (H 2 O 2 ) in the abscess area, catalase (CAT), an enzyme that triggers H 2 O 2 decomposition to generate O 2 , 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.