Nanophotosensitisers based on Cyclodextrin with Antimicrobial Photodynamic Action

New broad-spectrum antimicrobial strategies, alternative to antibiotics and able to efficiently to kill pathogens without inducing resistance, is one of the main objectives in public health. Antimicrobial photodynamic therapy (aPDT), based on the light-induced production of reactive oxygen species from photosensitizers (PS), is attracting growing interest to infection treatment, also including biofilm destruction. Photosensitiser nanosystems, so-called nanophotosensitisers (nanoPS), are currently developed to address the drawbacks due the limitation of single photoactive molecules such as the lack of solubility and stability in the biological media, biocompatibility, bioavailability, selectivity in the target tissue and stimuli-responsiveness upon triggers for controlled release of the photosensitiser. Here we will discuss different nanoPS releasing systems studied in our research labs based on the cationic porphyrin (N-methyl- 4-pyridyl)-21H,23H-porphyrin (TMPyP)) assembled with two different cyclodextrins (CDs), namely the trade sulfobutylether-beta-cyclodextrin (CAPTISOL®) and CD nanosponge (βNS) [1,2]. Nanoassemblies were prepared in ultrapure water by mixing PS and CDs, by exploiting their mutual electrostatic interaction, and characterized by various spectroscopic techniques such as UV/Vis, Steady-State and Time Resolved Fluorescence, Dynamic Light Scattering and ζ-potential. NanoPSs produced appreciable amount of single oxygen similar to free porphyrin and a prolonged stability after 6 days of incubations in physiological conditions and following photoirradiation. Antimicrobial photodynamic action of TMPyP/ βNS against fatal hospital-acquired infections such as P. aeruginosa and S. aureus was investigated by pointing out the ability of cationic porphyrin loaded-CD nanosponges to photo-kill bacterial cells at prolonged time of incubation and following irradiation. Moreover, nanoPS based on CAPTISOL® and TMPyP with photodynamic features exhibited photo-antimicrobial activity against Gramnegative and Gram-positive bacteria. Results from P. aeruginosa reveal that CAPTISOL® alone inhibits pyocyanin (PYO) production, also affecting bacterial biofilm formation. Finally, we obtained a synergistic effect of inhibition and destruction of P. aeruginosa biofilm by using the combination of CAPTISOL® and TMPyP.