Captisol® / porphyrin nanocomplexes for pathogens sensing and antimicrobial photodynamic therapy

Emerging antimicrobial therapeutic and disinfectant strategies are currently developed to efficiently inactivate pathogens without inducing resistance. Antimicrobial photodynamic therapy (aPDT), based on the light-induced production of reactive oxygen species from photosensitizers (PS), is attracting increasing interest in bacterial infection treatment, also including biofilm destruction. Moreover, the detection and monitoring of pathogen bacteria in water resources is a current challenging issue. Within our ongoing research on phototherapeutics and photodiagnostics, here we propose complexes based on the trade sulfobutylether-beta-cyclodextrin (Captisol®) entrapping the cationic porphyrin (N-methyl-4-pyridyl)-21H,23H-porphyrin (H2T4) [1,2] as nanomaterials for sensing and therapy. Nanocomplexes were prepared at different Captisol®/porphyrin molar ratio, at high entrapment efficiency in aqueous solution by solvent evaporation method and characterized by UV-Vis and Steady -State Fluorescence Emission, Dynamic Light Scattering and zeta-potential. In order to fabricate a diagnostic kit for pathogen sensing, stability of the nanocomplexes was studied in ultrapure and simulated sea water, in different containers and temperatures mimicking selected sea basins. The interaction of nanocomplexes with a wild strain of E.coli isolated from waste water was also investigated for bacterial sensing purpose. Finally, complexes photostability was monitored in PBS at pH=7.4 for applications in aPDT. Nanocomplexes with photodynamic features exhibited photo-antimicrobial and antibiofilm activity on Pseudomonas aeruginosa and Staphylococcus Aureus bacteria, in addition to generally sustained release properties and a higher photostability. All these results open the way to the development of novel nanotherapeutics and nanodiagnostics based on cyclodextrin and porphyrins. 1. Castriciano, M. A.; Zagami, R.; Casaletto, M. Martel, B.; Trapani, M.; Romeo, A.; Villari, V.;Sciortino, M. T.; Grasso, L.; Gugliemino, S.; Monsù Scolaro, L. and A. Mazzaglia,Biomacromolecules, 2017, 18, 1134-1144. 2. Zagami, R.; Franco, D.; Pipkin, J. D.; Antle, V.; De Plano, L.; Patanè, S.; Guglielmino, S.; MonsùScolaro, L. A. Mazzaglia A., Int. J. Pharm., 2020, 585, 119487.