Over the last 20 years, the number of pathogenic multi-resistant microorganisms has grown steadily, which has stimulated the search for new strategies to combat antimicrobial resistance. Antimicrobial photodynamic therapy (aPDT), also called photodynamic inactivation, is emerging as a promising alternative to treatments based on conventional antibiotics. We have explored the effectiveness of methylene blue-loaded targeted mesoporous silica nanoparticles (MSNP) in the photodynamic inactivation of two Gram negative bacteria, namely Escherichia coli and Pseudomonas aeruginosa. For E. coli, nanoparticle association clearly reduced the dark toxicity of MB while preserving its photoinactivation activity. For P. aeruginosa, a remarkable difference was observed between amino- and mannose-decorated nanoparticles. The details of singlet oxygen production in the nanoparticles have been characterized, revealing the presence of two populations of this cytotoxic species. Strong quenching of singlet oxygen within the nanoparticles is observed.

Reaction of porphycene isothiocyanates with primary and secondary amines leads to the formation of thiazolo[4,5-c]porphycenes, with a substantial shift in the absorption and fluorescence spectra. The conjugates show fluorescence in the near-infrared and are capable of photosensitizing the production of the cytotoxic species singlet oxygen.

Different silica-protoporphyrin IX (PpIX) nanocomposites have been synthesized to evaluate the dependence of singlet oxygen production and bacterial inactivation efficiency on the morphology of the nanomaterials. Modulation of the synthetic procedure allowed obtaining silica nanoparticles with different porosity which were characterized by TEM and spectroscopic analysis after PpIX adsorption. Time-resolved phosphorescence measurements on the different nanoporous samples revealed that the porosity of the nanoparticles plays a pivotal role on the singlet oxygen production and release from the nanoparticles. Thus, apart from the expected decay of singlet oxygen outside the silica matrix, a second component has been observed for the porous materials, attributed to the decay of singlet oxygen inside the pores. The relative efficiency of singlet oxygen production resulted to be higher for the sample with the greatest pores volume. The capability of the nanocomposites to inactivate bacteria was tested in vitro on Staphylococcus aureus strain. Interestingly, the efficiency for singlet oxygen production of the nanocomposites and their bacterial inactivation efficiency followed a different trend, indicating that the relative position of the photosensitizer and the superficial properties of the particles affect the antibacterial activity of the overall system.

Production of singlet molecular oxygen by photosensitisation remains the most common and convenient means of producing this non-radical yet highly-reactive oxygen species that participates in many chemical and biological processes. The details of singlet oxygen photosensitisation by organic dyes are well understood as well as its limitations. Novel materials and biomaterials with unprecedented optical, photophysical, and biological properties, as well as novel chemical and biological technologies have recently emerged that provide new opportunities for the controlled generation and delivery of singlet oxygen in biological media as well as for its detection and monitoring. This review summarises such novel contributions, ranging from stimulus-responsive switchable molecular photosensitisers to proteins as novel photoactive biotherapeutic drugs to metallic nanostructures as plasmonic antennas for singlet oxygen.

2-Aminothiazolo[4,5-c]porphycenes are a novel class of 22-π electron aromatic porphycene derivatives prepared by click reaction of porphycene isothiocyanates with primary and secondary amines with high potential as near-infrared theranostic labels. Herein, the optical and photophysical properties of 2-aminothiazolo[4,5-c]porphycenes have been studied, revealing a strong dependence on hydrogen bond donor solvents and acids. High hydrogen bond donor solvents and acids shift the absorption and fluorescence emission of 2-aminothiazolo[4,5-c]porphycenes to the blue due to a contraction of their aromatic system from 22-π to 18-π electrons. Finally, the aromatic shift has been successfully used to measure the pH using 2-aminothiazoloporphycene-labelled gold nanoclusters, paving the way for the use of these compounds as near infrared pH-sensitive probes.