Development of a hybrid CuS-ICG polymeric photosensitive vector and its application in antibacterial photodynamic therapy

At the present time, owing to the extremely high growth of microbial resistance to antibiotics and, consequently, the increased healthcare associated costs and the loss of efficacy of current treatments, the development of new therapies against bacteria is of paramount importance. For this reason, in this work, a hybrid synergetic nanovector has been developed, based on the encapsulation of a NIR (near infrared) photosensitive molecule (indocyanine green, ICG) in biodegradable polymeric nanoparticles (NPs). In addition, copper sulfide nanoparticles (CuS NPs), optically sensitive to NIR, were anchored on the polymeric nanoparticle shell in order to boost the generation of reactive oxygen species (ROS) upon NIR irradiation. As a result, the nanohybrid synthesized material is capable to generate ROS on demand when exposed to a NIR laser (808 nm) allowing for the repeated triggering of ROS production upon NIR light exposure. After each irradiation, the ROS generated were able to eliminate pathogenic bacteria, as it was demonstrated in-vitro with three bacterial strains, Staphylococcus aureus ATCC 25923 used as a reference strain (S. aureus), S. aureus USA300 (methicillin-resistant strain, MRSA) and GFP-expressing antibiotic-sensitive S. aureus (methicillin-sensitive strain, MSSA). Finally, the effect of the hybrid NPs in the skin bed was tested on a plasma-derived in vitro skin model. Fluorescence and histological images showed the presence of CuS NPs all over the dermal layer lacking epidermis of the skin construct. Thus, the in vitro model facilitated the prediction of the nanovector’s behavior in a human skin equivalent, showcasing its potential application against topical infections after wounding.