This work reports the photophysical and biological evaluation of five cationic porphyrins as photosensitizers (PS) for the photodynamic inactivation (PDI) of Penicillium chrysogenum conidia. Two different cationic porphyrin groups were synthesized from 5,10,15,20-tetrakis(4-pyridyl)porphyrin and 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin. The photostability and singlet oxygen generation studies showed that these molecules are photostable and efficient singlet oxygen generators. PDI experiments of P. chrysogenum conidia conducted with 50 μmol L(-1) of photosensitiser under white light at a fluence rate of 200 mW cm(-2) over 20 min showed that the most effective PS caused a 4.1 log reduction in the concentration of viable conidia. The present results show that porphyrins 1a and 1b are more efficient PSs than porphyrin 2a while porphyrins 1c and 2b show no inactivation of P. chrysogenum. It is also clear that the effectiveness of the molecule as PS for antifungal PDI is strongly related with the porphyrin substituent groups, and consequently their solubility in physiological media. The average amount of PS adsorbed per viable conidium was a determining factor in the photoinactivation efficiency and varied between the different studied PSs. Cationic PSs 1a and 1b might be promising anti-fungal PDI agents with potential applications in phytosanitation, biofilm control, bioremediation, and wastewater treatment.

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In this study, the novel biomimetic aerogel-based composite scaffolds through a synergistic combination of wet chemical synthesis and advanced engineering approaches have successfully designed. To this aim, initially the photo-crosslinkable methacrylated silk fibroin (SF-MA) biopolymer and methacrylated hollow mesoporous silica microcapsules (HMSC-MA) as the main constituents of the novel composite aerogels were synthesized. Afterward, by incorporation of drug-loaded HMSC-MA into the self-assembled SF-MA, printable gel-based composite inks are developed. By exploiting micro-extrusion-based three-dimensional (3D) printing, SF-MA-HMSC composite gels are printed by careful controlling their viscosity to provide a means to control the shape fidelity of the resulted printed gel constructs. The developed scaffold has shown a multitude of interesting biophysical and biological performances. Namely, thanks to the photo-crosslinking of the gel components during the 3D printing, the scaffolds become mechanically more stable than the pristine SF scaffolds. Also, freeze-casting the printed constructs generates further interconnectivity in the printed pore struts resulting in the scaffolds with hierarchically organized porosities necessary for cell infiltration and growth. Importantly, HMSC incorporated scaffolds promote antibacterial drug delivery, cellular ingrowth and proliferation, promoting osteoblastic differentiation by inducing the expression of osteogenic markers and matrix mineralization. Finally, the osteoconductive, -inductive, and anti-infective composite aerogels are expected to act as excellent bone implanting materials with an extra feature of local and sustained release of drug for efficient therapy of bone-related diseases.

Photodynamic inactivation (PDI) is an efficient approach against a wide range of microorganisms and can be viewed as an alternative for the treatment of microbial infections. In this work we synthesized "first" and "second" generation photosensitizers (PSs), the tetra-cationic porphyrin and the new penta-cationic chlorin , respectively, and evaluated their efficiency against two antibiotic resistant bacterial strains, Staphylococcus aureus and Pseudomonas aeruginosa. The PS was obtained in very good yield by an easy synthesis method. The PDI studies were performed in parallel with 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra-iodide (), a widely studied PS in PDI, and the obtained results were compared. Two different light ranges were used: white light (400-800 nm) and red light (530-800 nm) delivered at a fluence rate of 150 mW cm(-2). The results show that both strains, even though antibiotic resistant, were efficiently inactivated by the three PSs, chlorin being the most effective. For the Gram positive bacterium S. aureus a 7.0 log reduction was observed after 5-10 min of irradiation, at a concentration of 0.5 μM, whereas for the Gram negative P. aeruginosa, similar photoinactivation occurred at a higher PS concentration (10 μM) and after a longer irradiation period (30 min). The synthetic chlorin can be regarded as promising for the treatment of bacterial infections under red light, which penetrates deeper in living tissues. The results of this study open the possibility to prepare a new series of chlorin-type derivatives to efficiently photoinactivate Gram (+) and (-) antibiotic resistant bacteria. The efficient PDI with the chlorin indicates high potential for the use of a scaffold in the preparation of new generation PSs based on cationic chlorin derivatives.

Phthalocyanines (Pc) are photoactive molecules that can absorb and emit light in a large range of the UV-Vis spectrum with recognized potential for medical applications. Considering the biomedical applications an important limitation of these compounds is their low solubility in water. The use of suitable pyridinium groups on Pc is a good strategy to solve this drawback and to make them more effective to photoinactivate Gram-negative bacteria via a photodynamic inactivation (PDI) approach. Herein, an easy synthetic access to obtain inverted tetra- and octa-methoxypyridinium phthalocyanines (compounds 5 and 6) and also their efficiency to photoinactivate a recombinant bioluminescent strain of Escherichia coli is described. The obtained results were compared with the ones obtained when more conventional thiopyridinium phthalocyanines (compounds 7 and 8) were used. This innovative study comparing thiopyridinium and inverted methoxypyridinium moieties on cationic Pc is reported for the first time taking into account the efficiency of singlet oxygen ((1)O2) generation, water solubility and uptake properties.

Antimicrobial photodynamic inactivation is becoming a promising alternative to control microbial pathogens. The combination of positively charged groups and carbohydrate moieties with porphyrin derivatives results in increased cell recognition and water solubility, which improves cell membrane penetration. However, the nature of the oxidative damage and the cellular targets of photodamage are still not clearly identified. This work reports the use of four cationic galactoporphyrins as PSs against two environmental bacteria, Micrococcus sp. and Pseudomonas sp., resistant to oxidative stress induced by UV-B exposure. The effect of (1)O(2) generated during the PDI assays on oxidation of cellular lipids and proteins was also assessed. PDI experiments with Micrococcus sp. and Pseudomonas sp. were conducted with 0.5 and 5.0 μmol L(-1) of photosensitiser, respectively, under white light at a fluence rate of 150 mW cm(-2) during 15 min. The most effective compounds against Gram (+) bacteria were PSs 3a, 5a and 6a leading to ≈8.0 log of photoinactivation while PSs 3a and 6a caused the highest inactivation (≈6.0 log and 5.3 log) of the Gram (-) strain. The adsorption to cellular material and (1)O(2) generation capacity of the PS molecule were determinant factors for these inactivation profiles. The occurrence of protein carbonylation and lipid peroxidation supports the hypothesis that antibacterial PDI is triggered by damage of external cell structures such as the cell wall and membrane.

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Among the several types of inorganic nanoparticles available, silica nanoparticles (SNP) have earned their relevance in biological applications namely, as bioimaging agents. In fact,°uorescent SNP (FSNP) have been explored in this¯eld as protective nanocarriers, overcoming some limitations presented by conventional organic dyes such as high photobleaching rates. A crucial aspect on the use of°uorescent SNP relates to their surface properties, since it determines the extent of interaction between nanoparticles and biological systems, namely in terms of colloidal stability in water, cellular recognition and internalization, tracking, biodistribution and specicity, among others. Therefore, it is imperative to understand the mechanisms underlying the interaction between biosystems and the SNP surfaces, making surface functionalization a relevant step in order to take full advantage of particle properties. The versatility of the surface chemistry on silica platforms, together with the intrinsic hydrophilicity and biocompatibility, make these systems suitable for bioimaging applications, such as those mentioned in this review.