This study focuses on the design and evaluation of a series of A2BC aminoporphyrins, featuring electron-donating substituents like pyrene, carbazole, and phenothiazine to enhance their photophysical and biological performance. Detailed characterization through spectroscopic methods, single-crystal X-ray diffraction, and computational analyses revealed insights into their electronic structure and planarity. Photophysical investigations revealed characteristic Soret and Q bands, along with tunable fluorescence and excited-state lifetimes influenced by the meso substituents. Biological evaluation was conducted using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and fluorescence microscopy to assess the photodynamic therapeutic efficacy against T24 bladder cancer cells. The porphyrins exhibited pronounced photocytotoxicity upon 660 nm light activation, attributed to reactive oxygen species (ROS) generation. Cellular analysis, including acridine orange/ethidium bromide and 4',6-diamidino-2-phenylindole staining, confirmed apoptosis induction through chromatin condensation and nuclear fragmentation. The findings highlight the potential of these porphyrins as effective photosensitizers for photodynamic therapy, demonstrating enhanced stability and ROS generation efficiency.

Photodynamic therapy has become a promising non-invasive method for the treatment of LSIL associated with HR-HPV infections. This literature review assesses the efficacy, safety, and clinical relevance of PDT for managing HPV-related cervical lesions. PDT employs photosensitizers, such as 5-aminolevulinic acid, which selectively accumulate in abnormal cervical tissues. When subjected to particular wavelengths of light, these agents become activated and produce reactive oxygen species, leading to the target elimination of particular cells. Numerous studies have documented the effectiveness of PDT with pathological regression rate improving to 94.79%, and the HR-HPV clearance rate increased to 93.75%. Beyond facilitating lesion regression, PDT also plays a significant role in eliminating persistent HR-HPV infections, which are a crucial element in the advancement of cervical dysplasia. Furthermore, the non-invasive nature of PDT presents a compelling alternative to traditional surgical approaches, which may compromise fertility and cause cervical stenosis. PDT is generally well-tolerated; adverse reactions are typically mild and transient, including symptoms such as abdominal discomfort and increased vaginal discharge. Most notably, the fertility-preserving characteristics of PDT render it an optimal treatment choice, particularly for young women desiring to maintain their reproductive potential. While the existing data is promising, it is essential to conduct additional research to enhance treatment protocols, optimize dosages, and thoroughly assess the long-lasting impact of photodynamic therapy in the field of gynecology. By synthesizing existing evidence, this review supports the enhanced incorporation of PDT into clinical decision-making frameworks for the management of HPV-related LSIL.

Iridium(III) complexes have been recognized as promising candidates for two-photon sensitized photodynamic therapy (PDT). In this context, we report on the study of two complexes: a monomer (IrL1) and a dimer (Ir2L2). Both complexes possess 2-phenylpyridine cyclometallating ligands and a pyridylbenzimidazole derivative as an ancillary ligand. In the dimer, the two Ir(III) centers are connected by a non-conjugated bridged bis(pyridylbenzimidazole). We compare the photophysical properties of these complexes. Both display phosphorescent emission in the orange-red part of the visible spectrum, with emissions centered at 610 nm for IrL1 and 625 nm for Ir2L2, both exhibiting quantum yields of ∼24%. However, Ir2L2 proves to be much brighter than the monomer, making the dimer four times brighter than IrL1. This trend is consistent under two-photon excitation (TPE), and the singlet oxygen generation quantum yields, with the dimer displaying a figure of merit (σTPA × ΦΔ) of 40, compared to only 5 for the monomer. Both complexes generate intracellular ROS and exhibit strong phototoxicity upon blue light activation (λ = 420 nm), achieving submicromolar IC50 values in HT29 and A549 cell lines after 24 h of incubation. Moreover, with TPE (λ = 800 nm), both complexes also generate intracellular ROS and induce cancer cell death.

Herein we compare the electronic structures of the Co(I), Co(II), and Co(III) phthalocyanines, which were elucidated using UV-vis-NIR and magnetic circular dichroism (MCD) spectroscopy as well as density functional theory (DFT) and time-dependent DFT (TDDFT) calculations. The NIR triplet-multiplet bands in PcR4(2-)CoIIL2 (L = nil, Py, or nBuNH2; R = H or tert-Bu) complexes were studied by MCD spectroscopy for the first time and compared to those reported earlier by us in PcR4(2-)Cu (R = tert-Bu or SO3Na) compounds (J. Porphyrins Phthalocyanines 2025, 29, 110-122). In all cases, a Faraday MCD pseudo A-term was observed for this transition. DFT and TDDFT calculations successfully explained a systematic blue-shift in the metal-to-ligand charge-transfer (MLCT) and B1-band transitions going from [PcR4(2-)CoI]- to PcR4(2-)CoIIL2 to [PcR4(2-)CoIIIX2]- (X = CN- or Br-) complexes. Additionally, absorption bands observed in the 370-530 nm spectral envelope in [PcR4(2-)CoIIIX2]- complexes were assigned with a high level of confidence for the first time. This work provides the first combined systematic experimental and theoretical study that highlights similarities and differences in (magneto)optical spectroscopy of cobalt phthalocyanines spanning three oxidation states at the central metal ion.

Open-shell radical materials, which are characterized by unpaired electrons, have led to revolutionary breakthroughs in material science due to their unique optoelectronic properties. However, the involvement of organic radicals in photodynamic therapy (PDT) has rarely been reported or discussed. This work studies two photosensitizer analogs. 4AM-OS with extended π-conjugation exhibits open-shell radical characters and enhanced type-I photodynamic activity compared with closed-shell 2AM-CS. 4AM-OS displays the thermally accessible triplet-state character, resulting in more unpaired electrons delocalized along the π-conjugated backbone at higher temperatures. Accordingly, the temperature-dependent photodynamic activity of 4AM-OS confirms its association with the open-shell electronic structure. As the unpaired electrons in open-shell 4AM-OS are more delocalized and generate additional electronic energy states, photo-induced charge transfer is promoted to facilitate type-I photodynamic reactions. This observation addresses the challenge associated with near-infrared (NIR) photosensitizers, such as 4AM-OS, which often demonstrate low efficacy in PDT due to the limited energy provided by NIR light despite its superior tissue penetration depth. Overall, clarifying the beneficial role of organic radicals in photodynamic reactions will bring revolutionary breakthroughs to developing high-performance NIR photosensitizers and promoting the efficacy of PDT for deep-seated lesions.

The main photophysical properties of recently synthesized Pd- and Pt-isocorroles, characterized and proposed as potential photosensitizers in photodynamic therapy, have been investigated and rationalized using density functional theory and its time-dependent formulation. Both the 5 and 10-(2-pyrrolyl)-5,10,15-tris(4-methylphenyl) isomers have been considered. In addition to determining the minimum energy structures of the ground and excited states, we have calculated the excitation energies, spin-orbit coupling constants, nonradiative intersystem crossing rate constants and two photons cross section. Also, the type I PDT mechanisms have been considered. Results show that the photoactivity of both Pd and Pt complexes mainly depends on their singlet-triplet energy gap, which is necessary to promote the O23 Σ g - → 1 Δ g ${{}^{{\rm { 3}}}{{\rm { \Sigma{}}}}_{{\rm { g}}}^{{\rm { -}}}\to {}^{1}{\Delta }_{g}}$ excitation. The study of the photophysical properties of the free ligands indicates that this trend is common for both the free and Pt- and Pd-isocorroles. The production of superoxide ions (O2 .(-)) is possible only for the 10-(2-pyrrolyl)-5,10,15-tris(4-methylphenyl) isomers.

Age-related macular degeneration (AMD) is a progressive degenerative disease that leads to visual impairment, predominantly affecting the elderly. Despite significant advancements in treatment, a definitive cure remains elusive. Current therapeutic strategies only slow down disease progression, inhibiting abnormal blood vessels growth, and preserving or improving vision. Among these strategies, photodynamic therapy (PDT) has emerged as a promising treatment, particularly for neovascular form, the most severe form of the disease. Although several photosensitizers (PS) have been developed, only one has received clinical approval for use in AMD. This treatment involves the intravenous administration of a photosensitizing agent that preferentially accumulates in the abnormal blood vessels beneath the macula. Upon activation by targeted laser light, the PS triggers photochemical reactions, leading to vascular occlusion and the reduction of choroidal neovascularization. This review provides a comprehensive overview of both experimental and clinical studies on PDT for AMD, discussing the current state of research, challenges in treatment optimization, and potential future directions to enhance this therapeutic approach.

Esophageal cancer is the eighth most common cancer worldwide and the sixth leading cause of cancer-related deaths. In this study, we propose a novel esophageal stent equipped with a wireless, battery-free, and movable photodynamic therapy (PDT) unit designed to treat esophageal tumors with flexibility, precision, and real-time control. This system integrates a PDT unit and an electrochemical pneumatic soft actuator into a conventional esophageal stent. Each module incorporates a piezoelectric transducer capable of receiving external ultrasound to power the respective module. These transducers selectively respond to different external ultrasound frequencies, enabling independent operation without mutual interference. The therapy module provides a light source for PDT, inducing the production of cytotoxic reactive oxygen species (ROS) in tumor cells and promoting apoptosis. The pneumatic actuator based on electrochemical principles plays a critical role in controlling the position of the PDT light source, enabling the movement of the therapy module up to 200 mm within 15 min. This allows real-time control to maintain the light source near the tumor, ensuring precise and targeted treatment. The system can wirelessly and in real-time control the PDT light source's position via external ultrasound, offering a novel approach for treating esophageal cancer patients according to the need of tumor's progression.

Photodynamic inactivation (PDI) has been revealed as a valuable approach against viral infections because of the fast therapeutic effect and low possibility of resistance development. The photodynamic inhibition of the infectivity of human herpes simplex virus type 1 (HSV-1) strain Victoria at different stages of its reproduction was studied. PDI activity was determined on extracellular virions, on the stage of their adsorption to the Madin-Darby bovine kidney (MDBK) cell line and inhibition of the viral replication stage by application of two tetra-methylpyridiloxy substituted gallium and zinc phthalocyanines (ZnPcMe and GaPcMe) upon 660 nm light exposure with a light-emitting diode (LED 660 nm). The PDI effect was evaluated on extracellular virions and virus adsorption by the terminal dilution method and the change in viral infectivity, which was compared to the untreated control group. The decrease in viral titer (Δlgs) was determined. The effect on the replicative cycle of the virus was determined using the cytopathic effect inhibition (CPE) assay. The direct influence on the virions showed a remarkable effect with a decrease in the viral titer more than 4 (Δlg > 4). The influence of the virus to the cell on the stage of adsorption was also significantly affected by the exposure time and the concentration of applied photosensitizers. A distinct inhibition was evaluated for ZnPcMe at the viral replication stage, which demonstrated a high photoinactivation index (PII = 33.0). This study suggested the high efficacy of PDI with phthalocyanines on HSV-1 virus, with full inhibition caused by the mechanism of singlet oxygen generation. These promising data are a good basis for further investigations on the PDI application against pathogenic viruses.

Photodynamic therapy (PDT) has been developed as a potential cancer treatment approach owing to its non-invasiveness, spatiotemporal control and limited side effects. Currently, great efforts have been made to improve the PDT effect in terms of safety and efficiency. In this review, we highlight recent advances in innovative strategies for enhanced PDT, including (1) the development of novel radicals, (2) design of activatable photosensitizers based on the TME and light, and (3) photocatalytic NADH oxidation to damage the mitochondrial electron transport chain. Additionally, the new mechanisms for PDT are also presented as an inspiration for the design of novel PSs. Finally, we discuss the current challenges and future prospects in the clinical practice of these innovative strategies. It is hoped that this review will provide a new angle for understanding the relationship between the intratumoural redox environment and PDT mechanisms, and new ideas for the future development of smart PDT systems.

Cancer therapy, from malignant tumor inhibition to cellular eradication treatment, remains a challenge, especially regarding reduced side effects and low energy consumption during treatment. Hence, phytochemicals as cytotoxic sensitizers or photosensitizers deserve special attention. The dark and photo-response of Yemenite 'Etrog' leaf extracts applied to prostate PC3 cancer cells is reported here. An XTT cell viability assay along with light microscope observations revealed pronounced cytotoxic activity of the extract for long exposure times of 72 h upon concentrations of 175 μg/mL and 87.5 μg/mL, while phototoxic effect was obtained even at low concentration of 10.93 μg/mL and a short introduction period of 1.5 h. For the longest time incubation of 72 h and for the highest extract concentration of 175 μg/mL, relative cell survival decreased by up to 60% (below the IC50). In combined phyto-photodynamic therapy, a reduction of 63% compared to unirradiated controls was obtained. The concentration of extract in cells versus the accumulation time was inversely related to fluorescence emission intensity readings. Extracellular ROS production was also shown. Based on an ATR-FTIR analysis of the powdered leaves and their liquid ethanolic extract, biochemical fingerprints of both polar and non-polar phyto-constituents were identified, thereby suggesting their implementation as phyto-medicine and phyto-photomedicine.

A DFT and TDDFT study has been carried out on monomeric anthraquinones Emodin and Dermocybin (Em, Derm) recently proposed as natural antibacterial photosensitizers able to act also against gram-negative microbes. The computational study has been performed considering the relative amount of neutral and ionic forms of each compound in water, with the variation of pH. The occurrence of both Type I and Type II photoreactions has been explored computing the absorption properties of each species, the spin-orbit coupling constants (SOC), the vertical ionization potentials and the vertical electron affinities. The most plausible deactivation channels leading to the population of excited triplet states have been proposed. Our data indicate Emodin as more active than Dermocybin in antimicrobial photodynamic therapy throughout the Type II mechanism. Our data support a dual TypeI/II activity of the monomeric anthraquinones Emodin and Dermccybin in water, in all the considered protonation states.

Enterococcus faecalis is among the most resistant bacteria found in infected root canals. The demand for cutting-edge disinfection methods has rekindled research on photoinactivation with visible light. This study investigated the bactericidal activity of femtosecond laser irradiation against vancomycin-resistant Enterococcus faecalis V583 (VRE). The effect of parameters such as wavelength and energy density on the viability and growth kinetics of VRE was studied to design an optimized laser-based antimicrobial photoinactivation approach without any prior addition of exogenous photosensitizers. The most effective wavelengths were 430 nm and 435 nm at a fluence of 1000 J/cm2, causing a nearly 2-log reduction (98.6% and 98.3% inhibition, respectively) in viable bacterial counts. The colony-forming units and growth rate of the laser-treated cultures were progressively decreased as energy density or light dose increased at 445 nm but reached a limit at 1250 J/cm2. At a higher fluence of 2000 J/cm2, the efficacy was reduced due to a photobleaching phenomenon. Our results highlight the importance of optimizing laser exposure parameters, such as wavelength and fluence, in bacterial photoinactivation experiments. To our knowledge, this is the first study to report an optimized wavelength for the inactivation of VRE using visible femtosecond laser light.

Singlet dioxygen has been widely applied in different disciplines such as medicine (photodynamic therapy or blood sterilization), remediation (wastewater treatment) or industrial processes (fine chemicals synthesis). Particularly, it can be conveniently generated by energy transfer between a photosensitizer's triplet state and triplet dioxygen upon irradiation with visible light. Among the best photosensitizers, substituted zinc(II) phthalocyanines are prominent due to their excellent photophysical properties, which can be tuned by structural modifications, such as halogen- and chalcogen-atom substitution. These patterns allow for the enhancement of spin-orbit coupling, commonly attributed to the heavy atom effect, which correlates with the atomic number ( Z ${Z}$ ) and the spin-orbit coupling constant ( ζ ${\zeta }$ ) of the introduced heteroatom. Herein, a fully systematic analysis of the effect exerted by chalcogen atoms on the photophysical characteristics (absorption and fluorescence properties, lifetimes and singlet dioxygen photogeneration), involving 30 custom-made β-tetrasubstituted chalcogen-bearing zinc(II) phthalocyanines is described and evaluated regarding the heavy atom effect. Besides, the intersystem crossing rate constants are estimated by several independent methods and a quantitative profile of the heavy atom is provided by using linear correlations between relative intersystem crossing rates and relative atomic numbers. Good linear trends for both intersystem crossing rates (S1-T1 and T1-S0) were obtained, with a dependency on the atomic number and the spin-orbit coupling constant scaling asZ 0 . 4 ${{Z}^{0.4}}$ andζ 0 . 2 ${{\zeta }^{0.2}}$ , respectively The trend shows to be independent of the solvent and temperature.

Targeted therapy has become crucial to modern translational science, offering a remedy to conventional drug delivery challenges. Conventional drug delivery systems encountered challenges related to solubility, prolonged release, and inadequate drug penetration at the target region, such as a tumor. Several formulations, such as liposomes, polymers, and dendrimers, have been successful in advancing to clinical trials with the goal of improving the drug's pharmacokinetics and biodistribution. Various stealth coatings, including hydrophilic polymers such as PEG, chitosan, and polyacrylamides, can form a protective layer over nanoparticles, preventing aggregation, opsonization, and immune system detection. As a result, they are classified under the Generally Recognized as Safe (GRAS) category. Serum, a biological sample, has a complex composition. Non-specific adsorption of chemicals onto an electrode can lead to fouling, impacting the sensitivity and accuracy of focused diagnostics and therapies. Various anti-fouling materials and procedures have been developed to minimize the impact of fouling on specific diagnoses and therapies, leading to significant advancements in recent decades. This study provides a detailed analysis of current methodologies using surface modifications that leverage the antifouling properties of polymers, peptides, proteins, and cell membranes for advanced targeted diagnostics and therapy in cancer treatment. In conclusion, we examine the significant obstacles encountered by present technologies and the possible avenues for future study and development.

In photodynamic therapy (PDT) treatment, heavy-atom-free photosensitizers (PSs) are a great source of singlet oxygen photosensitizer. Reactive oxygen species (ROS) are produced by an energy transfer from the lowest energy triplet excited state to the molecular oxygen of cancer cells. To clarify the photophysical characteristics in the excited states of a few experimentally identified thionated (>C=S) molecules and their oxygenated congeners (>C=O), a quantum chemical study is conducted. This study illustrates the properties of the excited states in oxygen congeners that render them unsuitable for PDT treatment. Concurrently, a hierarchy is presented based on the utility of the lowest-energy triplet excitons of thionated compounds. Their non-radiative decay rates are calculated for reverse-ISC and inter-system crossover (ISC) processes. In addition, the vibronic importance of C=O and C=S bonds is clarified by the computation of the Huang-Rhys factor, effective vibrational mode, and reorganization energy inside the Marcus-Levich-Jörtner system. ROS generation in thionated PSs exceeds their oxygen congeners as kf ≪ kISC, where radiative decay rate is designated as kf. As a result, the current work offers a calculated strategy for analyzing the effectiveness of thionated photosensitizers in PDT.

Speckle patterns are a generic feature in coherent imaging techniques like optical coherence tomography (OCT). Although speckles are granular like noise texture, which degrades the image, they carry information that can be benefited by processing and thereby furnishing crucial information of sample structures, which can serve to provide significant important structural details of samples in in vivo longitudinal pre-clinical monitoring and assessments. Since the motions of tissue molecules are indicated through speckle patterns, speckle variance OCT (SV-OCT) can be well-utilized for quantitative assessments of speckle variance (SV) in biological tissues. SV-OCT has been acknowledged as a promising method for mapping microvasculature in transverse-directional blood vessels with high resolution in micrometers in both the transverse and depth directions. The fundamental scope of this article reviews the state-of-the-art and clinical benefits of SV-OCT to assess biological tissues for pre-clinical applications. In particular, focus on precise quantifications of in vivo vascular response, therapy assessments, and real-time temporal vascular effects of SV-OCT are primarily emphasized. Finally, SV-OCT-incorporating pre-clinical techniques with high potential are presented for future biomedical applications.

Photosensitizer (PS) with enhanced fluorescence is attractive for image-guided photodynamic therapy (PDT) due to its dual functional role in Singlet Oxygen Generation (SOG) and producing high fluorescence signals. Here, Eosin-Y (Ey) decorated polymer coated gold nanorods (GNRs) of different aspect ratios are synthesized and introduced as novel plasmon-enhanced nano-photosensitizers for this purpose. We show, upon excitation at 519 nm, simultaneous enhancement in fluorescence and SOG was achieved for the hybrid nanostructure. The best enhancement factors of 110 and 18 for metal-enhanced fluorescence and metal-enhanced SOG, respectively, are obtained with GNRs of length 133 nm and width 45 nm, where Ey is positioned at 12.6 nm from the metal core using layer-by-layer assembly of oppositely charged polymers. The observed plasmonic effect is critically analysed by comparing the near field damping rate along with decay length, far field scattering and nonradiative energy transfer of the nanohybrids.

The increase of bacterial resistance to antibiotics is a growing concern worldwide and the search for new therapies could cost billions of dollars and countless lives. Inert surfaces are major sources of contamination due to easier adhesion and formation of bacterial biofilms, hindering the disinfection process. Therefore, the objective of this study was to develop a photoactivatable and anti-adhesive kappa-carrageenan coating using proanthocyanidin as a photosensitizer. The complete reduction (>5-log10 CFU/cm3) of culturable cells of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa pathogens was achieved after 30 min of exposure to visible light (420 nm; 30 mW/cm2) with 5 % (w/v) of the photosensitizer. Cell membrane damage was confirmed by measuring potassium leakage, epifluorescence microscopy and bacterial motility analysis. Overall, visible light irradiation on coated solid surfaces mediated by proanthocyanidin showed no cytotoxicity and inactivated clinically important pathogens through the generation of reactive oxygen species, inhibiting bacterial initial adhesion. The developed coating is a promising alternative for a wide range of applications related to surface disinfection and food biopreservation.

Investigating combined treatment methodologies is crucial for addressing the complex nature of cancer. As an emerging strategy, nano-biotechnology encourages the design of unique nanocarriers possessing simultaneous therapeutic application properties. This study aims to explore the combined effects of photodynamic and anticancer treatments using a multifunctional nanocarrier system co-administering the photosensitizer IR780 and the anticancer agent curcumin (Cur) on lung cancer cells. Nanocarriers were prepared by encapsulation IR780 and Cur inside polyethylene glycol-capped mesoporous silica nanoparticles (Cur&IR780@MSN). Various concentrations of nanocarriers were evaluated on A549 cells following 5 min NIR laser light (continuous wave, 785 nm, 500 mW/cm2) irradiation. The internalization of nanocarriers was observed through the fluorescence of Cur. Changes in cell viability were determined using the MTT assay and AO/PI staining. A scratch assay analysis was also performed to examine the impact of combined treatments on cell migration. Characterization of the nanocarriers revealed adequate hydrophobic drug loading, temperature-inhibited feature, enhanced reactive oxygen species generation, a pH-dependent curcumin release profile, and high biocompatibility. Cur&IR780@MSN, which enabled the observation of synergistic treatment efficacy, successfully reduced cell viability by up to 78%. In contrast, monotherapies with curcumin-loaded nanocarriers (Cur@MSN) and IR780-loaded nanocarriers (IR780@MSN) resulted in a 38% and 56% decrease in cell viability, respectively. The constructed Cur&IR780@MSN nanocarrier has demonstrated remarkable performance in the application of combination therapies for lung cancer cells. These nanocarriers have the potential to inspire future studies in tumor treatment methods.

Reprogramming immunosuppressive M2 macrophages into M1 macrophages in tumor site provides a new strategy for the immunotherapy of colorectal cancer. In this study, M1 macrophage-derived exosome nanoprobe (M1UC) with Ce6-loaded upconversion material is designed to enhance the photodynamic performance of Ce6 while reprogramming M2 macrophages at tumor site and producing NO gas for three-mode synergistic therapy. Under the excitation of near-infrared light at 808 nm, the probe can generate 660 nm up-conversion fluorescence, which enables the photosensitizer Ce6 to produce ROS efficiently. In addition, the probe leads the production of NO by nitric oxide synthase on exosomes. Confocal laser and flow cytometry results show that M1UC probe reprograms M2 macrophages into M1 macrophages with an efficiency of 95.12%. The cell experiments show that the apoptosis rate of the three-mode synergistic therapy group is 78.8%, and the therapeutic effect is significantly higher than those of the other single treatment groups. In vivo experiments results show that M1UC probes maximally gather at the tumor site after 12 h of intravenous injection in orthotopic colorectal cancer mice. After 808 nm laser irradiation, the survival rate of mice is 100% and the recurrence rate was 0 within 60 d, and the therapeutic effect is significantly higher than those of other single treatment groups, which is also confirmed by immunohistochemistry. This M1 macrophage-derived exosome nanoplatform which is based on the three modes of immunotherapy, gas therapy and photodynamic therapy, provides a new design idea for the diagnosis and treatment of deep tumors.

Novel hybrid TiO2-based materials were obtained by adsorption of two different porphyrins on the surface of nanoparticles-commercially available 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and properly modified metalloporphyrin-5,10,15,20-tetrakis(2,6-difluoro-3-sulfophenyl)porphyrin palladium(II) (PdF2POH). The immobilization of porphyrins on the surface of TiO2 was possible due to the presence of sulfonyl groups. To further elevate the adsorption of porphyrin, an anchoring linker-4-hydroxybenzoic acid (PHBA)-was used. The synthesis of hybrid materials was proven by electronic absorption spectroscopy, dynamic light scattering (DLS), and photoelectrochemistry. Results prove the successful photosensitization of TiO2 to visible light by both porphyrins. However, the presence of the palladium ion in the modifier structure played a key role in strong adsorption, enhanced charge separation, and thus effective photosensitization. The incorporation of halogenated metalloporphyrins into TiO2 facilitates the enhancement of the comprehensive characteristics of the investigated materials and enables the evaluation of their performance under visible light. The effectiveness of reactive oxygen species (ROS) generation was also determined. Porphyrin-based materials with the addition of PHBA seemed to generate ROS more effectively than other composites. Interestingly, modifications influenced the generation of singlet oxygen for TPPS but not hydroxyl radical, in contrast to PdF2POH, where singlet oxygen generation was not influenced but hydroxyl radical generation was increased. Palladium (II) porphyrin-modified materials were characterized by higher photostability than TPPS-based nanostructures, as TPPS@PHBA-P25 materials showed the highest singlet oxygen generation and may be oxidized during light exposure. Photocatalytic activity tests with two model pollutants-methylene blue (MB) and the opioid drug tramadol (TRML)-confirmed the light dose-dependent degradation of those two compounds, especially PdF2POH@P25, which led to the virtually complete degradation of MB.

Triple negative breast cancer (TNBC) is a subtype of breast cancer characterised by its high tumourigenic, invasive, and immunosuppressive nature. Photodynamic therapy (PDT) is a focal therapy that uses light to activate a photosensitizing agent and induce a cytotoxic effect. 5-aza-2'-deoxycytidine (5-ADC) is a clinically approved immunomodulatory chemotherapy agent. The mechanism of the combination therapy using PDT and 5-ADC in evoking an anti-tumour response is not fully understood.

The present study examined whether a single dose of 5-ADC enhances the cytotoxic and anti-tumour immune effect of low dose PDT with verteporfin as the photosensitiser in a TNBC orthotopic syngeneic murine model, using the triple negative murine mammary tumour cell line 4T1. Histopathology analysis, digital pathology and immunohistochemistry of treated tumours and distant sites were assessed. Flow cytometry of splenic and breast tissue was used to identify T cell populations. Bioinformatics were used to identify tumour immune microenvironments related to TNBC patients.

Functional experiments showed that PDT was most effective when used in combination with 5-ADC to optimize its efficacy. 5-ADC/PDT combination therapy elicited a synergistic effect in vitro and was significantly more cytotoxic than monotherapies on 4T1 tumour cells. For tumour therapy, all types of treatments demonstrated histopathologically defined margins of necrosis, increased T cell expression in the spleen with absence of metastases or distant tissue destruction. Flow cytometry and digital pathology results showed significant increases in CD8 expressing cells with all treatments, whereas only the 5-ADC/PDT combination therapy showed increase in CD4 expression. Bioinformatics analysis of in silico publicly available TNBC data identified BCL3 and BCL2 as well as the following anti-tumour immune response biomarkers as significantly altered in TNBC compared to other breast cancer subtypes: GZMA, PRF1, CXCL1, CCL2, CCL4, and CCL5. Interestingly, molecular biomarker assays showed increase in anti-tumour response genes after treatment. The results showed concomitant increase in BCL3, with decrease in BCL2 expression in TNBC treatment. In addition, the treatments showed decrease in PRF1, CCL2, CCL4, and CCL5 genes with 5-ADC and 5-ADC/PDT treatment in both spleen and breast tissue, with the latter showing the most decrease.

To our knowledge, this is the first study that shows which of the innate and adaptive immune biomarkers are activated during PDT related treatment of the TNBC 4T1 mouse models. The results also indicate that some of the immune response biomarkers can be used to monitor the effectiveness of PDT treatment in TNBC murine model warranting further investigation in human subjects.

Food colorants are commonly used as excipients in pharmaceutical and nutraceutical fields, but they have a wide range of other potential applications, for instance, as cytotoxic drugs or mediators of physical antimicrobial treatments. The photodynamic antibacterial activity of several edible food colorants is reported here, including E127, E129, E124, E122, E133, and E150a, alongside Rhein, a natural lipophilic antibacterial and anticancer compound found in medicinal plants. Minimal inhibitory concentration (MIC) values for S. aureus and E. coli showed that E127 and Rhein were effective against both bacteria, while other colorants exhibited low activity against E. coli. In some cases, dark pre-incubation of the colorants with Gram-positive S. aureus increased their photodynamic activity. Adding Rhein to E127 increased the photodynamic activity of the latter in a supportive mode. Optional sensing mechanism pathways of combined E127/Rhein action were suggested. The antibacterial activity of the studied colorants can be ranged as follows: E127/Rhein >> E127 >> E150a > E122 > E124 >> E129 ≈ E133. E127 was also found to exhibit photodynamic properties. Short ultrasonic treatment before illumination caused intensification of E127 photodynamic activity against E. coli when applied alone and especially in combination with Rhein. Food colorants exhibiting photo- and sonodynamic properties may have good potential in food preservation.

Photodynamic therapy (PDT), a rapidly developing method for the treatment of cancer and bacterial diseases, is based on the photosensitization of oxygen to generate reactive oxygen species (ROS) that destroy specific biological targets. Among the various photosensitizers, phthalocyanines (Pc) have attracted particular attention due to their excellent photophysical properties, most of which meet the therapeutic requirements. The statement that aggregation of Pc-based photosensitizers is undesirable because it suppresses ROS generation has become commonplace in PDT. In this review, we have collected and discussed a number of works whose results refute this well-established axiom and show that aggregated forms of phthalocyanines can still exhibit photodynamic activity, in some cases in synergy with the photothermal and optoacoustic effects. In addition, ROS generation can be induced by aggregates under the conditions of sonodynamic therapy.

Effective photodynamic therapy (PDT) requires photosensitizers (PSs) to massively generate type I reactive oxygen species (ROS) in a less oxygen-dependent manner in the hypoxia tumor microenvironment. Herein, we present a cascade strategy to boost type I ROS, especially hydroxyl radical (OH·-), generation with an aggregation-induced emission (AIE) photosensitizer-albumin complex for hypoxia-tolerant PDT. The cationic AIE PS TPAQ-Py-PF6 (TPA = triphenylamine, Q = anthraquinone, Py = pyridine) contains three important moieties to cooperatively enhance free radical generation: the AIE-active TPA unit ensures the effective triplet exciton generation in aggregate, the anthraquinone moiety possesses the redox cycling ability to promote electron transfer, while the cationic methylpyridinium cation further increases intramolecular charge transfer and electron separation processes. Inserting the cationic TPAQ-Py-PF6 into the hydrophobic domain of bovine serum albumin nanoparticles (BSA NPs) could greatly immobilize its molecular geometry to further increase triplet exciton generation, while the electron-rich microenvironment of BSA ultimately leads to OH·- generation. Both experimental and theoretical results confirm the effectiveness of our molecular cationization and BSA immobilization cascade strategy for enhancing OH·- generation. In vitro and in vivo experiments validate the excellent antitumor PDT performance of BSA NPs, superior to the conventional polymeric encapsulation approach. Such a multidimensional cascade strategy for specially boosting OH·- generation shall hold great potential in hypoxia-tolerant PDT and related antitumor applications.

Cyclodextrins (CDs) are cyclic oligosaccharides that contain a relatively hydrophobic central cavity and a hydrophilic outer surface. They are widely used to form non-covalent inclusion complexes with many substances. Although such inclusion complexes typically exhibit higher aqueous solubility and chemical stability than pure drugs, it has been shown that CDs can promote the degradation of some drugs. This property of stabilizing certain drugs while destabilizing others can be explained by the type of CD used and the structure of the inclusion complex formed. In addition, the ability to form complexes of CDs can be improved through the addition of suitable auxiliary substances, forming multicomponent complexes. Therefore, it is important to evaluate the effect that binary and multicomponent complexes have on the chemical and physical stability of complexed drugs. The objective of this review is to summarize the studies on the stabilizing and destabilizing effects of complexes with CDs on drugs that exhibit stability problems.

Photodynamic therapy (PDT) is a clinically approved minimally/non-invasive treatment modality that has been used to treat various conditions, including cancer. The bystander and abscopal effects are two well-documented significant reactions involved in imparting long-term systemic effects in the field of radiobiology. The PDT-induced generation of reactive oxygen and nitrogen species and immune responses is majorly involved in eliciting the bystander and abscopal effects. However, the results in this regard are unsatisfactory and unpredictable due to several poorly elucidated underlying mechanisms and other factors such as the type of cancer being treated, the irradiation dose applied, the treatment regimen employed, and many others. Therefore, in this review, we attempted to summarize the current knowledge regarding the non-targeted effects of PDT. The review is based on research published in the Web of Science, PubMed, Wiley Online Library, and Google Scholar databases up to June 2023. We have highlighted the current challenges and prospects in relation to obtaining clinically relevant robust, reproducible, and long-lasting antitumor effects, which may offer a clinically viable treatment against tumor recurrence and metastasis. The effectiveness of both targeted and untargeted PDT responses and their outcomes in clinics could be improved with more research in this area.

Throughout the world, oral cancer is a common and aggressive malignancy with a high risk of morbidity, mortality, and recurrence. The importance of early detection in cancer prevention and disease treatment cannot be overstated. Conventional therapeutic strategies have minor difficulties but considerable side effects and unfavourable consequences in clinical applications. Hence, there is a requirement for effective ways for early detection and treatment of oral cancer. At present, numerous forms of nanoparticles have piqued researchers' interest as a potentially useful tool for diagnostic probes and medicinal devices. Because of their inherent physicochemical properties and customizable surface modification, they are able to circumvent some of restrictions and accomplish the intended diagnostic and therapeutic impact. Nanotechnology is a unique field that has revolutionised the industry and is paving the way for new treatments for oral cancer. It can help with a better diagnosis with less harmful substances and is setting current guidelines for treatment. The use of nanotechnology in cancer diagnosis, therapy, and care improves clinical practise dramatically. The different types of nanoparticles that have been developed for the diagnosis and therapy of oral cancers will be covered in this study. The difficulties and potential uses of nanoparticles in the treatment and diagnosis of oral cancer are then highlighted. In order to emphasise existing difficulties and potential remedies for oral cancer, a prospective view of the future is also provided.

Cancer immunotherapy is a promising antitumor approach, whereas nontherapeutic side effects, tumor microenvironment (TME) intricacy, and low tumor immunogenicity limit its therapeutic efficacy. In recent years, combination immunotherapy with other therapies has been proven to considerably increase antitumor efficacy. However, achieving codelivery of the drugs to the tumor site remains a major challenge. Stimulus-responsive nanodelivery systems show controlled drug delivery and precise drug release. Polysaccharides, a family of potential biomaterials, are widely used in the development of stimulus-responsive nanomedicines due to their unique physicochemical properties, biocompatibility, and modifiability. Here, the antitumor activity of polysaccharides and several combined immunotherapy strategies (e.g., immunotherapy combined with chemotherapy, photodynamic therapy, or photothermal therapy) are summarized. More importantly, the recent progress of polysaccharide-based stimulus-responsive nanomedicines for combination cancer immunotherapy is discussed, with the focus on construction of nanomedicine, targeted delivery, drug release, and enhanced antitumor effects. Finally, the limitations and application prospects of this new field are discussed.

Photodynamic therapy (PDT) is a promising anticancer noninvasive technique that relies on the generation of reactive oxygen species (ROS). Unfortunately, PDT still has many limitations, including the resistance developed by cancer cells to the cytotoxic effect of ROS. Autophagy, which is a stress response mechanism, has been reported as a cellular pathway that reduces cell death following PDT. Recent studies have demonstrated that PDT in combination with other therapies can eliminate anticancer resistance. However, combination therapy is usually challenged by the differences in the pharmacokinetics of the drugs. Nanomaterials are excellent delivery systems for the efficient codelivery of two or more therapeutic agents. In this work, we report on the use of polysilsesquioxane (PSilQ) nanoparticles for the codelivery of chlorin-e6 (Ce6) and an autophagy inhibitor for early- or late-stage autophagy. Our results, obtained from a reactive oxygen species (ROS) generation assay and apoptosis and autophagy flux analyses, demonstrate that the reduced autophagy flux mediated by the combination approach afforded an increase in the phototherapeutic efficacy of Ce6-PSilQ nanoparticles. We envision that the promising results in the use of multimodal Ce6-PSilQ material as a codelivery system against cancer pave the way for its future application with other clinically relevant combinations.

The large number of deaths induced by carcinoma and infections indicates that the need for new, better, targeted therapy is higher than ever. Apart from classical treatments and medication, photodynamic therapy (PDT) is one of the possible approaches to cure these clinical conditions. This strategy offers several advantages, such as lower toxicity, selective treatment, faster recovery time, avoidance of systemic toxic effects, and others. Unfortunately, there is a small number of agents that are approved for usage in clinical PDT. Novel, efficient, biocompatible PDT agents are, thus, highly desired. One of the most promising candidates is represented by the broad family of carbon-based quantum dots, such as graphene quantum dots (GQDs), carbon quantum dots (CQDs), carbon nanodots (CNDs), and carbonized polymer dots (CPDs). In this review paper, these new smart nanomaterials are discussed as potential PDT agents, detailing their toxicity in the dark, and when they are exposed to light, as well as their effects on carcinoma and bacterial cells. The photoinduced effects of carbon-based quantum dots on bacteria and viruses are particularly interesting, since dots usually generate several highly toxic reactive oxygen species under blue light. These species are acting as bombs on pathogen cells, causing various devastating and toxic effects on those targets.

Antimicrobial resistance is an ever-growing global concern, making the development of alternative antimicrobial agents and techniques an urgent priority to protect public health. Antimicrobial photodynamic therapy (aPDT) is one such promising alternative, which harnesses the cytotoxic action of reactive oxygen species (ROS) generated upon irradiation of photosensitisers (PSs) with visible light to destroy microorganisms. In this study we report a convenient and facile method to produce highly photoactive antimicrobial microparticles, exhibiting minimal PS leaching, and examine the effect of particle size on antimicrobial activity. A ball milling technique produced a range of sizes of anionic p(HEMA-co-MAA) microparticles, providing large surface areas available for electrostatic attachment of the cationic PS, Toluidine Blue O (TBO). The TBO-incorporated microparticles showed a size-dependent effect on antimicrobial activity, with a decrease in microparticle size resulting in an increase in the bacterial reductions achieved when irradiated with red light. The >6 log₁₀Pseudomonas aeruginosa and Staphylococcus aureus reductions (>99.9999%) achieved within 30 and 60 min, respectively, by TBO-incorporated >90 μm microparticles were attributed to the cytotoxic action of the ROS generated by TBO molecules bound to the microparticles, with no PS leaching from these particles detected over this timeframe. TBO-incorporated microparticles capable of significantly reducing the bioburden of solutions with short durations of low intensity red light irradiation and minimal leaching present an attractive platform for various antimicrobial applications.

This proceeding article compiles current research on the development of boron delivery drugs for boron neutron capture therapy that was presented and discussed at the National Cancer Institute (NCI) Workshop on Neutron Capture Therapy that took place on April 20-22, 2022. The most used boron sources are icosahedral boron clusters attached to peptides, proteins (such as albumin), porphyrin derivatives, dendrimers, polymers, and nanoparticles, or encapsulated into liposomes. These boron clusters and/or carriers can be labeled with contrast agents allowing for the use of imaging techniques, such as PET, SPECT, and fluorescence, that enable quantification of tumor-localized boron and their use as theranostic agents.

Natural compounds originated from plants and microorganisms and their combinations are currently being investigated as a possible treatment for several diseases including cancer. Hypericin (photodynamically-active pigment from Hypericum perforatum L.) and manumycin A (inhibitor of farnesyltransferase from Streptomyces parvulus) belong to the chemicals potentially applicable in clinical practice. In this study we evaluated potential cytotoxic (via trypan blue exclusion test), genotoxic (via DNA-topology and comet assays), and mutagenic effects (via bacterial reverse mutation test) of these compounds and their combinations considering the molecular mechanism of their action in cell-free and cellular systems. Our results did not reveal neither cytotoxic nor mutagenic activities of tested compounds and their combinations. Regarding the genotoxic potential, no damage of plasmid DNA in cell-free system was detected. On the other hand, photoactivated hypericin and manumycin A were able to induce primary DNA damage in human lymphocytes analyzed by comet assay. The possible antagonistic interactions between these two metabolites were estimated using SynergyFinder software analysis and experimental data obtained from comet assay. Our findings indicate that not only the presence of substances, but also their ratio plays an important role in resulting effects of the combined treatment in cellular system.

This manuscript presents the first report on antimicrobial photo-inactivation in vitro using tetra-cationic porphyrins with peripheral platinum(II) bipyridyl complexes against Gram-positive bacteria. Two isomeric tetra-cationic porphyrins (3TPyP and 4TPyP) were tested against clinically important bacterial species. The antimicrobial activity assays were performed at specific photosensitizer (PS) concentrations under dark and white-light LED irradiation conditions for 120 min. The porphyrin 3-PtTPyP was the most efficient PS against the bacteria tested, inhibiting bacterial growth in just 15 min and 30 min at low concentrations (3.75 and 0.45 µM). The minimal inhibitory concentration of the porphyrin increased in the presence of reactive oxygen species scavengers, indicating that singlet oxygen and radical species likely participated in the photo-oxidation mechanism. In addition, the checkerboard assay that tests the association of compounds, showed a synergistic effect, suggesting a potentiation of the antibacterial effect when porphyrin was tested in combination with ciprofloxacin and vancomycin. Thus, tetra-cationic porphyrins containing platinum(II) complexes are promising agents for microbial photo-inactivation as an alternative therapy against infections.

Photodynamic therapy is a non-invasive therapeutic strategy that combines external light with a photosensitizer (PS) to destroy abnormal cells. Despite the great progress in the development of new photosensitizers with improved efficacy, the PS's photosensitivity, high hydrophobicity, and tumor target avidity still represent the main challenges. Herein, newly synthesized brominated squaraine, exhibiting intense absorption in the red/near-infrared region, has been successfully incorporated into Quatsome (QS) nanovesicles at different loadings. The formulations under study have been characterized and interrogated in vitro for cytotoxicity, cellular uptake, and PDT efficiency in a breast cancer cell line. The nanoencapsulation of brominated squaraine into QS overcomes the non-water solubility limitation of the brominated squaraine without compromising its ability to generate ROS rapidly. In addition, PDT effectiveness is maximized due to the highly localized PS loadings in the QS. This strategy allows using a therapeutic squaraine concentration that is 100 times lower than the concentration of free squaraine usually employed in PDT. Taken together, our results reveal the benefits of the incorporation of brominated squaraine into QS to optimize their photoactive properties and support their applicability as photosensitizer agents for PDT.

The successful clinical application of immune checkpoint blockade (ICB) and chimeric antigen receptor T cells (CAR-T) therapeutics has attracted extensive attention to immunotherapy, however, their drawbacks such as limited specificity, persistence and toxicity haven't met the high expectations on efficient cancer treatments. Therapeutic cancer vaccines which instruct the immune system to capture tumor specific antigens, generate long-term immune memory and specifically eliminate cancer cells gradually become the most promising strategies to eradicate tumor. However, the disadvantages of some existing vaccines such as weak immunogenicity and in vivo instability have restricted their development. Nanotechnology has been recently incorporated into vaccine fabrication and exhibited promising results for cancer immunotherapy. Nanoparticles promote the stability of vaccines, as well as enhance antigen recognition and presentation owing to their nanometer size which promotes internalization of antigens by phagocytic cells. The surface modification with targeting units further permits the delivery of vaccines to specific cells. Meanwhile, nanocarriers with adjuvant effect can improve the efficacy of vaccines. In addition to classic vaccines composed of antigens and adjuvants, the nanoparticle-mediated chemotherapy, radiotherapy and certain other therapeutics could induce the release of tumor antigens in situ, which therefore effectively simulate antitumor immune responses. Such vaccine-like nanomedicine not only kills primary tumors, but also prevents tumor recurrence and helps eliminate metastatic tumors. Herein, we introduce recent developments in nanoparticle-based delivery systems for antigen delivery and in situ antitumor vaccination. We will also discuss the remaining opportunities and challenges of nanovaccine in clinical translation towards cancer treatment.

Bladder cancer is the first cancer for which PDT was clinically approved in 1993. Unfortunately, it was unsuccessful due to side effects like bladder contraction. Here, we summarized the recent progress of PDT for bladder cancers, focusing on photosensitizers and formulations. General strategies to minimize side effects are intravesical administration of photosensitizers, use of targeting strategies for photosensitizers and better control of light. Non-muscle invasive bladder cancers are more suitable for PDT than muscle invasive and metastatic bladder cancers. In 2010, the FDA approved blue light cystoscopy, using PpIX fluorescence, for photodynamic diagnosis of non-muscle invasive bladder cancer. PpIX produced from HAL was also used in PDT but was not successful due to low therapeutic efficacy. To enhance the efficacy of PpIX-PDT, we have been working on combining it with singlet oxygen-activatable prodrugs. The use of these prodrugs increases the therapeutic efficacy of the PpIX-PDT. It also improves tumor selectivity of the prodrugs due to the preferential formation of PpIX in cancer cells resulting in decreased off-target toxicity. Future challenges include improving prodrugs and light delivery across the bladder barrier to deeper tumor tissue and generating an effective therapeutic response in an In vivo setting without causing collateral damage to bladder function.

Typically, nanomedicine was prepared using a nanocarrier to load cargo for specific purposes. In this work, a carrier-free nanosystem for imaging and photodynamic (PDT)/chemo combination therapy was developed using simple self-assembly of a dye and a chemotherapeutic agent. The resulting nanoparticles (I₂-IR783/MTX@NPs) exhibited a spherical morphology with a size of 240.6 ± 2.5 nm. I₂-IR783/MTX@NPs had substantial internalization in 4T1 murine breast cancer cells and showed a synergistic anticancer effect after NIR light irradiation. Additionally, the 3D tumor model exhibits the same phototoxicity of nanoparticles as a 2D cell culture. The PDT efficiency of the nanosystem in the physiological environment was confirmed by the detection of intracellular reactive oxygen species as well as the live/dead viability/cytotoxicity assay following NIR light exposure. In addition, optical coherence tomography (OCT) was used as an alternative tool to monitor the response after treatment. Therefore, I₂-IR783/MTX@NPs show great potential use in theranostic application for breast cancer PDT-chemotherapy.

In photodynamic therapy (PDT), the uses of nanoparticles bearing photosensitizers (PSs) can overcome some of the drawbacks of using a PS alone (e.g., poor water solubility and low tumor selectivity). However, numerous nano-formulations are developed by physical encapsulation of PSs through Van der Waals interactions, which have not only a limited load efficiency but also some in vivo biodistribution problems caused by leakage or burst release. Herein, polymersomes made from an amphiphilic block copolymer, in which a PS with aggregation-induced emission (AIE-PS) is covalently attached to its hydrophobic poly(amino acid) block, are reported. These AIE-PS polymersomes dispersed in aqueous solution have a high AIE-PS load efficiency (up to 46% as a mass fraction), a hydrodynamic diameter of 86 nm that is suitable for in vivo applications, and an excellent colloidal stability for at least 1 month. They exhibit a red/near-infrared photoluminescence and ability to generate reactive oxygen species (ROS) under visible light. They are non-cytotoxic in the dark as tested on Hela cells up to concentration of 100 µm. Benefiting from colloidal stability, AIE property and ROS generation capability, such a family of polymersomes can be great candidates for image-guided PDT.

Despite specialists' efforts to find the best solutions for cancer diagnosis and therapy, this pathology remains the biggest health threat in the world. Global statistics concerning deaths associated with cancer are alarming; therefore, it is necessary to intensify interdisciplinary research in order to identify efficient strategies for cancer diagnosis and therapy, by using new molecules with optimal therapeutic potential and minimal adverse effects. This review focuses on studies of porphyrin macrocycles with regard to their structural and spectral profiles relevant to their applicability in efficient cancer diagnosis and therapy. Furthermore, we present a critical overview of the main commercial formulations, followed by short descriptions of some strategies approached in the development of third-generation photosensitizers.

This updated review aims to describe the current status in the development of liposome-based systems for the targeted delivery of phthalocyanines for photodynamic therapy (PDT). Although a number of other drug delivery systems (DDS) can be found in the literature and have been studied for phthalocyanines or similar photosensitizers (PSs), liposomes are by far the closest to clinical practice. PDT itself finds application not only in the selective destruction of tumour tissues or the treatment of microbial infections, but above all in aesthetic medicine. From the point of view of administration, some PSs can advantageously be delivered through the skin, but for phthalocyanines, systemic administration is more suitable. However, systemic administration places higher demands on advanced DDS, active tissue targeting and reduction of side effects. This review focuses on the already described liposomal DDS for phthalocyanines, but also describes examples of DDS used for structurally related PSs, which can be assumed to be applicable to phthalocyanines as well.

Photodynamic antimicrobial chemotherapy (PACT) is extensively studied as a strategic method to inactivate pathogenic microbes in wastewater for addressing the limitations associated with chlorination, ozonation, and ultraviolet irradiation as disinfection methods, which generally promote the development of resistant genes and harmful by-products such as trihalomethanes. PACT is dependent on photons, oxygen, and a photosensitizer to induce cytotoxic effects on various microbes by generating reactive oxygen species. Photosensitizers such as porphyrins have demonstrated significant microbial inactivation through PACT, hence now explored for wastewater phototreatment. This review aims to evaluate the efficacy of porphyrins and porphyrin-conjugates as photosensitizers for wastewater photoinactivation. Concerns relating to the application of photosensitizers in water treatment are also evaluated. This includes recovery and reuse of the photosensitizer when immobilized on solid supports.