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

Abstract Pathogenic bacteria induce 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 sites, the therapeutic efficacy of oxygen consuming PDT has been limited. Herein, a transdermal delivery system is reported to allow effective delivery of photosensitizers into infected skin for PDT treatment of skin infections by bacteria. Considering the overproduction 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 Staphylococcus Aureus . After screening a series of fluorinated low molecular weight polyethylenimine (F‐PEI) with different fluorination degrees, the optimized F‐PEI formulation is identified with the best transdermal delivery ability system. Upon mixing, the formed Ce6‐CAT@F‐PEI nanocomplex shows effective transdermal penetration after being applied to the skin surface. With light exposure of the infected skin, highly effective in vivo anti‐bacterial PDT therapeutic effect with Ce6‐CAT@F‐PEI is observed. This work proposes a transdermal PDT therapeutic nanomedicine particularly promising for the anti‐bacterial treatment of skin infections.