Bacteria-Targeted Theranostics Combining Two-Photon Imaging and Photodynamic Therapy for Infection Control and Wound Healing – MSN-2hv

Microbial infections of the skin and underlying tissues are among the most frequent conditions encountered in actuating ambulatory care. Staphylococcus aureus (S. aureus) is the causative agent for the majority of primary skin infections. Wound related infections of the skin, especially when associated with co-morbid conditions and/or bacteraemia, can lead to severe complications and prolonged hospital admissions; in some cases, they can be even mortal. Owing to the lack of permeation of most antibiotic agents into the deep skin layers and subdermal tissues from conventional topical preparations, deep skin infections generally do not respond well to external therapy with antibiotics and are therefore usually treated by oral or parenteral antibiotics with high doses. During the course of treatment, there is a significant incidence of side-effects, allergic reactions and patient inconvenience, all of which highly influence the treatment efficiency. The MSN-2hv project proposes an innovative alternative treatment approach. It concerns the development of two-photon responsive mesoporous silica-based nanostructures loaded with photosensitizers and/or other anti-pathogenic drugs to fight such bacterial infections and to induce efficient wound healing. Indeed, two-photon excitation provides a spatio-temporal resolution combined with the high penetration of the laser beam for a very efficient imaging and therapy of wounds. A series of photosensitizer/antibiotic-loaded silica nanoparticles, including Mesoporous Silica Nanoparticles (MSN), Hollow Mesoporous Silica Nanoparticles (HMSN), and Periodic Mesoporous Organosilica Nanoparticles (PMON) will be formulated. Their feasibility for two-photon photodynamic therapy (PDT) bacterial treatment as well as two-photon fluorescence imaging will be demonstrated in MSN-2hv. A strong emphasis will be given to the assessment of toxicity, biocompatibility, biodegradability, and biodistribution of the new antibacterial nanostructures in vitro (Fibroblasts, Macrophages, and HUVEC) and in vivo in zebrafish and mice. The effectiveness to treat wound-infections by S. aureus will be tested and evaluated using in vitro and in vivo approaches. It is hoped that this new possibility to treat deep dermal infections will help to overcome the current limitations.