Porphyrin Photosensitizers Grafted in Cellulose Supports: A Review.

Cellulose is the most abundant natural biopolymer and owing to its compatibility with biological tissues, it is considered a versatile starting material for developing new and sustainable materials from renewable resources. With the advent of drug-resistance among pathogenic microorganisms, recent strategies have focused on the development of novel treatment options and alternative antimicrobial therapies, such as antimicrobial photodynamic therapy (aPDT). This approach encompasses the combination of photoactive dyes and harmless visible light, in the presence of dioxygen, to produce reactive oxygen species that can selectively kill microorganisms. Photosensitizers for aPDT can be adsorbed, entrapped, or linked to cellulose-like supports, providing an increase in the surface area, with improved mechanical strength, barrier, and antimicrobial properties, paving the way to new applications, such as wound disinfection, sterilization of medical materials and surfaces in different contexts (industrial, household and hospital), or prevention of microbial contamination in packaged food. This review will report the development of porphyrinic photosensitizers supported on cellulose/cellulose derivative materials to achieve effective photoinactivation. A brief overview of the efficiency of cellulose based photoactive dyes for cancer, using photodynamic therapy (PDT), will be also discussed. Particular attention will be devoted to the synthetic routes behind the preparation of the photosensitizer-cellulose functional materials.

Porphyrin-Based Compounds: Synthesis and Application.

Porphyrin-based compounds are an attractive and versatile class of molecules that have attracted significant attention across different scientific disciplines [...].

Sulfonamide Porphyrins as Potent Photosensitizers against Multidrug-Resistant Staphylococcus aureus (MRSA): The Role of Co-Adjuvants.

Sulfonamides are a conventional class of antibiotics that are well-suited to combat infections. However, their overuse leads to antimicrobial resistance. Porphyrins and analogs have demonstrated excellent photosensitizing properties and have been used as antimicrobial agents to photoinactivate microorganisms, including multiresistant Staphylococcus aureus (MRSA) strains. It is well recognized that the combination of different therapeutic agents might improve the biological outcome. In this present work, a novel meso-arylporphyrin and its Zn(II) complex functionalized with sulfonamide groups were synthesized and characterized and the antibacterial activity towards MRSA with and without the presence of the adjuvant KI was evaluated. For comparison, the studies were also extended to the corresponding sulfonated porphyrin TPP(SO3H)4. Photodynamic studies revealed that all porphyrin derivatives were effective in photoinactivating MRSA (>99.9% of reduction) at a concentration of 5.0 µM upon white light radiation with an irradiance of 25 mW cm-2 and a total light dose of 15 J cm-2. The combination of the porphyrin photosensitizers with the co-adjuvant KI during the photodynamic treatment proved to be very promising allowing a significant reduction in the treatment time and photosensitizer concentration by six times and at least five times, respectively. The combined effect observed for TPP(SO2NHEt)4 and ZnTPP(SO2NHEt)4 with KI seems to be due to the formation of reactive iodine radicals. In the photodynamic studies with TPP(SO3H)4 plus KI, the cooperative action was mainly due to the formation of free iodine (I2).

The challenging combination of intense fluorescence and high singlet oxygen quantum yield in photostable chlorins--a contribution to theranostics.

High fluorescence quantum yields, high singlet oxygen quantum yields and intense absorptions in the phototherapeutic window are fundamental properties for compounds intended for fluorescence diagnosis and photodynamic therapy. We report on photostable chlorins that combine these properties. The fluorinated tetraphenylchlorin FCMet has ΦF = 0.396 and ΦΔ = 0.58 ± 0.07, whereas F2CMet has ΦF = 0.360 and ΦΔ = 0.54 ± 0.05, and both have molar absorption coefficients larger than 30,000 M(-1) cm(-1) above 650 nm. These dual functional agents use nearly all the energy absorbed to perform the desired functions and are appropriate for theranostics applications.

Photomodulation Approaches to Overcome Antimicrobial Resistance.

Photopharmacology is an approach that aims to be an alternative to classical chemotherapy. Herein, the different classes of photoswitches and photocleavage compounds and their biological applications are described. Proteolysis targeting chimeras (PROTACs) containing azobenzene moieties (PHOTACs) and photocleavable protecting groups (photocaged PROTACs) are also mentioned. Furthermore, porphyrins are referenced as successful photoactive compounds in a clinical context, such as in the photodynamic therapy of tumours as well as preventing antimicrobial resistance, namely in bacteria. Porphyrins combining photoswitches and photocleavage systems are highlighted, taking advantage of both photopharmacology and photodynamic action. Finally, porphyrins with antibacterial activity are described, taking advantage of the synergistic effect of photodynamic treatment and antibiotic therapy to overcome bacterial resistance.

Photodynamic inactivation of microorganisms in different water matrices: The effect of physicochemical parameters on the treatment outcome.

Wastewater (WW) insufficiently treated for the disinfection of microorganisms, including pathogenic ones, is a source of concern and a possible generator of public health problems. Traditional disinfection methods to reduce pathogens concentration (e.g., chlorination, ozonation, UV) are expensive, unsafe, and/or sometimes ineffective, highlighting the need for new disinfection technologies. The promising results of photodynamic inactivation (PDI) treatment to eradicate microorganisms suggest the efficacy of this treatment to improve WW quality. This work aimed to assess if PDI can be successfully extended to real contexts for the microbial inactivation in WW. For the first time, PDI experiments with 9 different water matrices compositions were performed to inquire about the influence of some of their physicochemical parameters on the effectiveness of microbial inactivation. Bacterial photoinactivation was tested in freshwater, aquaculture water, and seawater samples, as well as in influents and effluents samples from domestic, industrial, and a mixture of industrial and domestic WW receiving wastewater treatment plants (WWTPs). Additionally, PDI assays were performed in phosphate-buffered saline isotonic solution (PBS), used as an aqueous comparative matrix. To relate the PDI disinfection efficiency with the physicochemical compositions of the different used water matrices, a series of statistical analysis were performed, in order to support our main conclusions. Overall, the results showed that PDI is an effective and promising alternative to traditionally used WW disinfection methods, with a bacterial reduction of >3.0 log CFU/mL in all the water matrices within the first hour of PDI treatment, but also that the physicochemical composition of the aqueous matrices to be PDI-disinfected must be taken into account since they seem to influence the PDI efficacy, namely the pH, with acidic pH conditions seeming to be associated to a better PDI performance in general.

On the singlet states of porphyrins, chlorins and bacteriochlorins and their ability to harvest red/infrared light.

The decay channels of the singlet excited states of halogenated sulfonamide tetraphenylporphyrins, chlorins and bacteriochlorins were fully characterized. It was found that the radiative rates and the internal conversion rates of the bacteriochlorins are lower than expected from the Strickler-Berg equation and from the energy-gap law, respectively. It is concluded that this family of bacteriochlorins can combine long-lived singlet states with photostability, which are desired properties to harvest near-infrared light.

Mechanisms of singlet-oxygen and superoxide-ion generation by porphyrins and bacteriochlorins and their implications in photodynamic therapy.

New halogenated and sulfonated bacteriochlorins and their analogous porphyrins are employed as photosensitizers of singlet oxygen and the superoxide ion. The mechanisms of energy and electron transfer are clarified and the rates are measured. The intermediacy of a charge-transfer (CT) complex is proved for bacteriochlorins, but excluded for porphyrins. The energies of the intermediates and the rates of their interconversions are measured, and are used to obtain the efficiencies of all the processes. The mechanism of formation of the hydroxyl radical in the presence of bacteriochlorins is proposed to involve a photocatalytic step. The usefulness of these photosensitizers in the photodynamic therapy (PDT) of cancer is assessed, and the following recommendations are given for the design of more effective PDT protocols employing such photosensitizers: 1) light doses should be given over a more extended period of time when the photosensitizers form CT complexes with molecular oxygen, and 2) Fe(2+) may improve the efficiency of such photosensitizers if co-located in the same cell organelle assisting with an in vivo Fenton reaction.

Photoacoustic measurement of electron injection efficiencies and energies from excited sensitizer dyes into nanocrystalline TiO2 films.

Time-resolved photoacoustic calorimetry is used to measure the energy released upon injection of an electron from an electronically excited dye adsorbed to nanocrystalline TiO2 into the conduction band of this material. More energy is released when the environment of the dye is made less polar, because the energy of the dye-oxidized state has a more pronounced solvent dependence than the edge of the conduction band of the TiO2 semiconductor. Such energy dependences should be considered in the design of more efficient dye-sensitized solar cells.

Synthesis, photophysical studies and anticancer activity of a new halogenated water-soluble porphyrin.

A water-soluble halogenated porphyrin, namely 5,10,15,20-tetrakis(2-chloro-3-sulfophenyl)porphyrin (TCPPSO(3)H), was prepared and evaluated as sensitizer for photodynamic therapy (PDT). Photophysical properties of TCPPSO(3)H, such as high photostability, long triplet lifetime and high singlet oxygen quantum yield suggest high effectiveness of this class of halogenated porphyrins in PDT. TCPPSO(3)H is non-toxic in the dark and causes a significant photodynamic effect examined against MCF7 (human breast carcinoma), SKMEL 188 (human melanoma) and S91(mouse melanoma) cell lines upon red light irradiation (cutoff < 600 nm) at low light doses. Time-dependent cellular uptake of TCPPSO(3)H reached plateau at 120 min and was the highest for S91, 20% lower for MCF7 and 70% lower for SKMEL 188. Our results show that this halogenated water-soluble porphyrin is an efficient photosensitizer and reveal the potential of this class of compounds as PDT agents.

Tissue uptake study and photodynamic therapy of melanoma-bearing mice with a nontoxic, effective chlorin.

Chlorins have intense red absorptions and high tumor affinities that make them interesting candidates for photodynamic therapy (PDT) of cancer. This paper reports cytotoxicity, phototoxicity, in vitro cellular uptake, and in vivo biodistribution and PDT efficacy of a synthetic chlorin derivative (TCPCSO3H) towards Cloudman melanoma cells (S91). No cytotoxic effects were observed in vitro at concentrations up to 20 µm, and no toxicity was observed in vivo in DBA mice with doses up to 2 mg kg⁻¹. Pharmacokinetics and biodistribution of TCPCSO3H were evaluated in vivo in DBA mice bearing S91 tumors. TCPCSO3H demonstrated preferential accumulation in S91 mouse melanoma, with tumor-to-normal tissue ratios of 5 and 11 for muscle and skin, respectively, 24 h after intravenous injection of 2 mg kg⁻¹. Photodynamic therapy performed under these conditions with 70 mW cm⁻² diode laser irradiation at 655 nm for 25 min (total light dose=105 J cm⁻²) resulted in scab formation, followed by temporary or permanent (>60 days) tumor remission. According to the Kaplan-Meier analysis, the median survival time of the control group was 9 days, whereas that of the treated group was 38 days.

New halogenated water-soluble chlorin and bacteriochlorin as photostable PDT sensitizers: synthesis, spectroscopy, photophysics, and in†vitro photosensitizing efficacy.

Chlorin and bacteriochlorin derivatives of 5,10,15,20-tetrakis(2-chloro-5-sulfophenyl)porphyrin have intense absorptions in the phototherapeutic window, high water solubility, high photostability, low fluorescence quantum yield, long triplet lifetimes, and high singlet oxygen quantum yields. Biological studies revealed their negligible dark cytotoxicity, yet significant photodynamic effect against A549 (human lung adenocarcinoma), MCF7 (human breast carcinoma) and SK-MEL-188 (human melanoma) cell lines upon red light irradiation (cutoff λ<600 nm) at low light doses. Time-dependent cellular accumulation of the chlorinated sulfonated chlorin reached a plateau at 2 h, as previously observed for the related porphyrin. However, the optimal incubation time for the bacteriochlorin derivative was significantly longer (12 h). The spectroscopic, photophysical, and biological properties of the compounds are discussed in relevance to their PDT activity, leading to the conclusion that the bacteriochlorin derivative is a promising candidate for future in vivo experiments.

A comparative study of water soluble 5,10,15,20-tetrakis(2,6-dichloro-3-sulfophenyl)porphyrin and its metal complexes as efficient sensitizers for photodegradation of phenols.

5,10,15,20-Tetrakis(2,6-dichloro-3-chlorosulfophenyl)porphyrin and its tin and zinc complexes were synthesized with high yields and fully characterized. The corresponding water-soluble 5,10,15,20-tetrakis(2,6-dichloro-3-sulfophenyl)porphyrins were obtained by hydrolysis with water. An extensive photophysical study of the new water soluble porphyrinic compounds was carried out including absorption and fluorescence spectra, fluorescence quantum yields, triplet absorption spectra, triplet lifetimes, triplet and singlet oxygen quantum yields. These sensitizers were successfully used in the photodegradation of 4-chlorophenol and 2,6-dimethylphenol. A comparison is made of their efficiencies, and some mechanistic considerations are highlighted.