Photosensitizers For Photodynamic Therapy Research Articles

A Copper Silicate-Based Multifunctional Nanoplatform with Glutathione Depletion and Hypoxia Relief for Synergistic Photodynamic/Chemodynamic Therapy.

Chemodynamic therapy (CDT) alone cannot achieve sufficient therapeutic effects due to the excessive glutathione (GSH) and hypoxia in the tumor microenvironment (TME). Developing a novel strategy to improve efficiency is urgently needed. Herein, we prepared a copper silicate nanoplatform (CSNP) derived from colloidal silica. The Cu(II) in CSNP can be reduced to Cu(I), which cascades to induce a subsequent CDT process. Additionally, benefiting from GSH depletion and oxygen (O2) generation under 660 nm laser irradiation, CSNP exhibits both Fenton-like and hypoxia-alleviating activities, contributing to the effective generation of superoxide anion radical (•O2-) and hydroxyl radical (•OH) in the TME. Furthermore, given the suitable band-gap characteristic and excellent photochemical properties, CSNP can also serve as an efficient type-I photosensitizer for photodynamic therapy (PDT). The synergistic CDT/PDT activity of CSNP presents an efficient antitumor effect and biosecurity in both in vitro and in vivo experiments. The development of an all-in-one nanoplatform that integrates Fenton-like and photosensing properties could improve ROS production within tumors. This study highlights the potential of silicate nanomaterials in cancer treatment.

Nitrogen-doped carbon quantum dots as antimicrobial agents against gram-positive Bacillus subtilis and Staphylococcus aureus under visible white light-emitting diode

Carbon nanomaterials, such as carbon quantum dots (CQDs), are excellent candidates for antibacterial agent development as they are cost-effective. Nitrogen-doped CQDs (N-doped CQDs) exhibit antibacterial activity against gram-positive bacteria. However, investigation of N-CQDs and their efficacy against the selected bacterial strains under visible light irradiation has not been carried out. Here, we aimed to evaluate N-CQDs for their efficacy as a photosensitizer for antimicrobial photodynamic therapy (aPDT). N-CQDs were synthesized using the hydrothermal method with 1,3,6-trinitropyrene (TNP) as the nitrogen and carbon source. Antimicrobial tests of N-CQDs were conducted against gram-positive (Bacillus subtilis NCIB 3610, Staphylococcus aureus Newman, and S. aureus USA300) and gram-negative (Escherichia coli K12) bacteria at different concentrations (0–100 mg/L). The N-CQDs exerted a moderate growth-inhibitory effect on gram-positive bacteria in the dark. However, in the presence of white light generated using 20-W light-emitting diode, N-CQDs could completely kill the bacteria at a low concentration of 20 mg/L. The minimal inhibitory concentration of N-CQDs for the two S. aureus strains (Newman and USA300) was 20 mg/L under light conditions, whereas that for B. subtilis was 100 mg/L. The results demonstrate that N-CQDs may be used as a photosensitizer in aPDT and as an antibacterial agent.

Synthesis and applications of metal organic frameworks in photodynamic therapy

Metal organic frameworks (MOFs) consist of metal atoms or clusters, coordinated to organic ligands to form macromolecular super structures, with pores large enough to host free drug molecules, including photodynamic therapy (PDT) photosensitizers. This review presents examples of applications in PDT of various types of MOFs. To contextualize the discussions of their PDT applications, general procedures of MOF synthesis are considered. Applications of MOFs in PDT are described using examples of several combination therapy innovations developed for the purpose of solving some of the key challenges in the clinical translation value chain of PDT. The review presents evidence to show that the explosion of research in MOFs is due to their capability for applications as carriers and delivery systems for PDT photosensitizers. It also shows their unique applications as platforms for combination therapies, for stimulus responsive release of photosensitizer and drug molecules, for cancer cell targeting, and for auxiliary enhancement of efficacy. Published literature on MOFs has been on the rise since the eighties. In Scopus, the applications of MOFs in PDT increased from 1 article in 2010, to 169 articles in 2023, whereas published literature on MOFs generally, increased from 878 to 11644 during this period. Research on the applications of MOFs in PDT has therefore increased more than that of MOFs generally. Literature on the applications of MOFs in PDT increased by between 0.7% to 1.45% relative to published literature on MOFs generally. Clearly, MOFs are researched to overcome challenges of and improve PDT efficacy, more than they are generally.

Synthesis and Evaluation of Novel meso-Tetraphenyltetrabenzoporphyrins for Photodynamic Therapy.

To discover effective photosensitizers for photodynamic therapy (PDT), a series of new meso-tetraphenyltetrabenzoporphyrin (m-Ph4TBP) derivatives were designed, prepared, and characterized. All m-Ph4TBPs own two characteristic absorption bands in the range of 450-500 and 600-700 nm and have the ability to generate singlet oxygen upon photoexcitation. Most of the m-Ph4TBPs demonstrated high photoactivity, among which compounds I4, I6, I12, and I13 induced apoptosis and also exhibited excellent photodynamic activities in vivo. Nonetheless, the liver organs of the I4 and I6-PDT groups showed clear calcifications, whereas the liver tissues of the other PDT groups showed no calcification. It was indicated that compared to phenolic m-Ph4TBPs, glycol m-Ph4TBPs exhibited superior biological safety in mice. According to comprehensive evaluations, m-Ph4TBP I12 displayed excellent photodynamic antitumor efficacy and biological safety and can be regarded as a promising antitumor drug candidate.

Poly Lactic-co-Glycolic Acid (PLGA) Loaded with a Squaraine Dye as Photosensitizer for Antimicrobial Photodynamic Therapy.

Antimicrobial Photodynamic Therapy (aPDT) is an innovative and promising method for combating infections, reducing the risk of antimicrobial resistance compared to traditional antibiotics. Squaraine (SQ) dyes can be considered promising photosensitizers (PSs) but are generally hydrophobic molecules that can self-aggregate under physiological conditions. To overcome these drawbacks, a possible solution is to incorporate SQs inside nanoparticles (NPs). The present work deals with the design and development of innovative nanophotosensitizers based on poly lactic-co-glycolic acid (PLGA) NPs incorporating a brominated squaraine (BrSQ) with potential application in aPDT. Two designs of experiments (DoEs) based on the single emulsion and nanoprecipitation methods were set up to investigate how different variables (type of solvent, solvent ratio, concentration of PLGA, stabilizer and dye, sonication power and time) can affect the size, zeta (ζ)-potential, yield, entrapment efficiency, and drug loading capacity of the SQ-PLGA NPs. SQ-PLGA NPs were characterized by NTA, FE-SEM, and UV-Vis spectroscopy and the ability to produce reactive oxygen species (ROS) was evaluated, proving that ROS generation ability is preserved in SQ-PLGA. In vitro antimicrobial activity against Gram-positive bacteria in planktonic state using Staphylococcus aureus was conducted in different conditions and pH to evaluate the potential of these nanophotosensitizers for aPDT in the local treatment of infections.

A Review on Future Prospects of Photosensitizers in Photodynamic Therapy

A Review on Future Prospects of Photosensitizers in Photodynamic Therapy

Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands

Ir(III) and Ru(II) polypyridyl complexes are promising photosensitizers (PSs) for photodynamic therapy (PDT) due to their outstanding photophysical properties. Herein, one series of cyclometallated Ir(III) complexes and two series of Ru(II) polypyridyl derivatives bearing three different thiazolyl-β-carboline N^N′ ligands have been synthesized, aiming to evaluate the impact of the different metal fragments ([Ir(C^N)2]+ or [Ru(N^N)2]2+) and N^N’ ligands on the photophysical and biological properties. All the compounds exhibit remarkable photostability under blue-light irradiation and are emissive (605 < λem < 720 nm), with the Ru(II) derivatives displaying higher photoluminescence quantum yields and longer excited state lifetimes. The Ir PSs display pKa values between 5.9 and 7.9, whereas their Ru counterparts are less acidic (pKa > 9.3). The presence of the deprotonated form in the Ir-PSs favours the generation of reactive oxygen species (ROS) since, according to theoretical calculations, it features a low-lying ligand-centered triplet excited state (T1 = 3LC) with a long lifetime. All compounds have demonstrated anticancer activity. Ir(III) complexes 1–3 exhibit the highest cytotoxicity in dark conditions, comparable to cisplatin. Their activity is notably enhanced by blue-light irradiation, resulting in nanomolar IC50 values and phototoxicity indexes (PIs) between 70 and 201 in different cancer cell lines. The Ir(III) PSs are also activated by green (with PI between 16 and 19.2) and red light in the case of complex 3 (PI = 8.5). Their antitumor efficacy is confirmed by clonogenic assays and using spheroid models. The Ir(III) complexes rapidly enter cells, accumulating in mitochondria and lysosomes. Upon photoactivation, they generate ROS, leading to mitochondrial dysfunction and lysosomal damage and ultimately cell apoptosis. Additionally, they inhibit cancer cell migration, a crucial step in metastasis. In contrast, Ru(II) complex 6 exhibits moderate mitochondrial activity. Overall, Ir(III) complexes 1–3 show potential for selective light-controlled cancer treatment, providing an alternative mechanism to chemotherapy and the ability to inhibit lethal cancer cell dissemination.

Recent Progress in Thermally Activated Delayed Fluorescence Photosensitizers for Photodynamic Therapy.

Photodynamic therapy (PDT) is a rapidly growing discipline that is expected to become an encouraging noninvasive therapeutic strategy for cancer treatment. In the PDT process, an efficient intersystem crossing (ISC) process for photosensitizers from the singlet excited state (S1) to the triplet excited state (T1) is critical for the formation of cytotoxic reactive oxygen species and improvement of PDT performance. Thermally activated delayed fluorescence (TADF) molecules featuring an extremely small singlet-triplet energy gap and an efficient ISC process represent an enormous breakthrough for the PDT process. Consequently, the development of advanced TADF photosensitizers has become increasingly crucial and pressing. The most recent developments in TADF photosensitizers aimed at enhancing PDT efficiency for bio-applications are presented in this review. TADF photosensitizers with water dispersibility, targeting ability, activatable ability, and two-photon excitation properties are highlighted. Furthermore, the future challenges and perspectives of TADF photosensitizers in PDT are proposed.

Acridinedione-phthalimide conjugates: Intramolecular electron transfer and singlet oxygen generation studies for optical and photodynamic therapy applications

We reported herein the synthesis, characterization of hybrid conjugates composed of phthalimide (Phth) and acridine-1,8-diones (Acr) for optical and medical applications. For the synthetic procedure, a three-step synthetic strategy has been utilized. The optical properties of the examined 1,8-acridinedione–phthalimide connected molecules (AcrPhth 1–5) have been examined utilizing various spectroscopic techniques, e.g., steady-state absorption and fluorescence, and time-correlated single photon counting. The steady-state absorption studies showed that AcrPhth 1–5 absorbs the light in the UV and visible region. The fluorescence studies of AcrPhth 1–5 exhibited significant fluorescence quenching compared to the acridinedione control compounds (Acr 1–5) suggesting the occurrence of electron-transfer reactions from the electron donating acridinedione moiety (Acr) to the electron accepting phthalimide moiety (Phth). The rate and efficiency of the electron-transfer reactions were determined from the fluorescence lifetime measurements indicating the fast electron-transfer processes of the covalently connected AcrPhth 1–5 conjugates. Computational studies supported the intramolecular electron-transfer reaction of AcrPhth conjugates using ab initio B3LYP/6-311G methods. In the optimized structures, the HOMO was found to be entirely located on the Acr entity, while the LUMO was found to be entirely on the Phth entity. Further, the synthesized compounds were tested as photosensitizers for generating the singlet oxygen species, which is a key factor in the photodynamic therapy (PDT) applications. The nanosecond laser flash measurements enable us to detect the triplet-excited states of examined Acr and AcrPhth conjugates, determining the triplet quantum yields, and direct detecting the singlet oxygen in an accurate way. From this observation, the singlet quantum yields were found to be in the range of 0.12–0.27 (for Acr 1–5) and 0.07–0.19 (for AcrPhth 1–5 conjugates). The molecular docking studies revealed that compound AcrPhth 2 exhibited high binding affinity with for key genes (p53, TOP2B, p38, and EGFR) suggesting its potential as a targeted anticancer therapy.Graphical abstractEfficient intramolecular electron-transfer reaction for the light harvesting conjugates! In addition, the conjugates can be used as good photosensitizers for PDT

CPP10-targeted photoactivatable MOF nanosystem for combined photodynamic Therapy−Chemotherapy of cancer

The annual prevalence of gastric cancer has increased in recent years. Curcumin (CUR) has shown great potential in the treatment of gastric cancer; however, its low bioavailability and poor efficacy hinder its widespread clinical application. Additionally, CUR has been found to be excellent photosensitizer in photodynamic therapy. In this study, the Fe-based metal-organic framework (MOF) Fe Tetrakis (4-carboxyphenyl) porphyrin (Fe-TCPP，FT) was used as a photosensitizer and mononuclear agent. The natural anti-tumor active ingredient CUR was loaded as both a chemotherapeutic agent and photosensitizer to form the nanoparticles CUR@FT (CF). Finally, a cell-penetrating peptide (CPP10) was modified on the surface of the nanoparticles to construct a drug delivery system (named CPP10-PEG@CUR@FT, CCF) that could actively target tumor cells while exerting a synergistic therapeutic effect of chemotherapy and photodynamic therapy. This can improve the efficacy of CUR as a chemotherapeutic drug or photosensitizer, and the high drug load and pH sensitivity of FT nanoparticles provide an excellent carrier for the efficient delivery of CUR. The polyethene glycol (PEG)-conjugated CPP10 (PEG-CPP10) coating allows nanoparticles to specifically target gastric cancer cells, significantly improving the absorption of nanoparticles in vivo and in vitro and improving biosafety. We evaluated the thermal stability, drug loading capacity, and safety of FT as a drug delivery vehicle. We also assessed the in vitro photodynamic performance and toxicity of various nanoparticles and the targeting and biocompatibility of CPP10-PEG@CUR@FT. CPP10-PEG@CUR@FT could specifically target tumor cells, and its effect on killing gastric cancer cells (MKN45) under light was much stronger than that of free CUR. Its toxicity and side effects to other organs and tissues are low, offering good biosafety. The experimental results showed that FT and CUR exerted synergistic effects on photodynamic therapy and chemotherapy. In summary, our novel CUR-loaded targeted nano drug delivery system offers significant advantages by combining photodynamic therapy and chemotherapy for tumor treatment. This approach introduces a new concept for integrating chemotherapy, photodynamic therapy and targeted drug delivery, potentially providing a new strategy for the clinical treatment of gastric cancer.

Polymer-DNA Carriers Co-Deliver Photosensitizer and siRNA for Light-Promoted Gene Transfection and Hypoxia-Relieved Photodynamic Therapy.

Photochemical internalization is an efficient strategy relying on photodynamic reactions to promote siRNA endosomal escape for the success of RNA-interference gene regulation, which makes gene-photodynamic combined therapy highly synergistic and efficient. However, it is still desired to explore capable carriers to improve the delivery efficiency of the immiscible siRNA and organic photosensitizers simultaneously. Herein, we employ a micellar nanostructure (PSNA) self-assembled from polymer-DNA molecular chimeras to fulfill this task. PSNA can plentifully load photosensitizers in its hydrophobic core simply by the nanoprecipitation method. Moreover, it can organize siRNA self-assembly by the densely packed DNA shell, which leads to a higher loading capacity than the typical electrostatic condensation method. The experimental results prove that this PSNA carrier can greatly facilitate siRNA escape from the endosome/lysosome and enhance transfection. Accordingly, the PSNA-administrated therapy exhibits a significantly improved anti-tumor efficacy owing to the highly efficient co-delivery capability.

Effect of photodynamic therapy with two photosensitizers on the microtensile bond strength of a universal adhesive to affected dentin

BackgroundThis study aimed to evaluate the impact of photodynamic therapy (PDT) using two photosensitizers, methylene blue and indocyanine green, on the microtensile bond strength of a universal adhesive to caries-affected dentin. MethodsThe occlusal enamel of 60 third molars was cut to expose the inner one-third of the dentin. Artificial caries were induced through a pH cycling process. The samples were divided into three groups: M (Methylene blue+ diode laser), I (Indocyanine green agents+ diode laser irradiation), and control. Each group was further divided into two subgroups according to the adhesive protocol (self-etch, total-etch). After restoring with Gradia composite resin, teeth were sectioned and exposed to 5000 thermal cycles. Microtensile bond strength was measured using a universal testing machine. The data were subjected to two- and one-way ANOVA and paired comparisons were performed by the Tamhane and Tukey tests. ResultsThe study found significant effects of the photosensitizer, etching pattern, and their interactions on the microtensile bond strength of composite resin to caries-affected dentin (P < 0.001). In the self-etching mode, PDT with indocyanine green exhibited significantly higher bond strength values compared to PDT with methylene blue (P = 0.001) and the control groups (P < 0.001). However, no significant differences were observed in the total-etch mode. (P = 0.54). ConclusionsThe etching mode played a more significant role in the bond strength when using the universal adhesive alongside PDT with methylene blue and indocyanine green. Employing two photosensitizers in PDT during the self-etch mode significantly increased the bond strength values.

Acceptor-planarized type I photosensitizer for lipid droplet-targeted two-photon photodynamic therapy by ferroptosis

Acceptor-planarized type I photosensitizer for lipid droplet-targeted two-photon photodynamic therapy by ferroptosis

Newly Designed Quasi-intrinsic Photosensitizers for Fluorescence Image-Guided Two-Photon Photodynamic Therapy with Type I/II Photoreactions.

In this work, a set of quasi-intrinsic photosensitizers are theoretically proposed based on the 2-amino-8-(1'-β-d-2'-deoxyribofuranosyl)-imidazo[1,2-α]-1,3,5-triazin-4(8H)-one (P), which could pair with the 6-amino-5-nitro-3-(1'-β-d-2'-deoxyribofuranosyl)-2(1H)-pyridone (Z) and keep the essential structural characters of nucleic acid. It is revealed that the ring expansion and electron-donating/electron-withdrawing substitution bring enhanced two-photon absorption and bright photoluminescence of these monomers, thereby facilitating the selective excitation and tumor localization through fluorescence imaging. However, instead of undergoing radiative transition (S1 → S0), the base pairing induced fluorescence quenching and rapid intersystem crossing (S1 → Tn) are observed and characterized by the reduced singlet-triplet energy gaps and large spin-orbit coupling values. To ensure the phototherapeutic properties of the considered base pairs in long-lived T1 state, we examined the vertical electron affinity as well as vertical ionization potential for production of superoxide anions via Type I photoreaction, and their required T1 energy (0.98 eV) to generate singlet oxygen 1O2 via Type II mechanism.

Hypericin-mediated photodynamic therapy inhibits metastasis and EMT of colorectal cancer cells by regulating RhoA-ROCK1 signaling pathway.

Colorectal cancer (CRC) is significantly contributed to global cancer mortality rates. Treating CRC is particularly challenging due to metastasis and drug resistance. There is a pressing need for new treatment strategies against metastatic CRC. Photodynamic therapy (PDT) offers a well-established, minimally invasive treatment option for cancer with limited side effects. Hypericin (HYP), a potent photosensitizer for PDT, has been documented to induce cytotoxicity and apoptosis in various types of cancers. However, there are few reports on the inhibitory effects of HYP-mediated PDT on the metastatic ability of CRC cells. Here, we evaluate the inhibitory effects of HYP-mediated PDT against metastatic CRC cells and define its underlying mechanisms. Wound-healing and Transwell assays show that HYP-mediated PDT suppresses migration and invasion of CRC cells. F-actin visualization assays indicate HYP-mediated PDT decreases F-actin formation in CRC cells. TEM assays reveal HYP-mediated PDT disrupts pseudopodia formation of CRC cells. Mechanistically, immunofluorescence and western blotting results show that HYP-mediated PDT upregulates E-cadherin and downregulates N-cadherin and Vimentin. HYP-mediated PDT also suppresses key EMT regulators, including Snail, MMP9, ZEB1 and α-SMA. Additionally, the expressions of RhoA and ROCK1 are downregulated by HYP-mediated PDT. Together, these findings suggest that HYP-mediated PDT inhibits the migration and invasion of HCT116 and SW620 cells by modulating EMT and RhoA-ROCK1 signaling pathway. Thus, HYP-mediated PDT presents a potential therapeutic option for CRC.

Dissecting Exciton Dynamics in pH-Activatable Long-Wavelength Photosensitizers for Traceable Photodynamic Therapy.

Tumor-specific activatable long-wavelength (LW) photosensitizers (PSs) show promise in overcoming the limitations of traditional photodynamic therapy (PDT), such as systemic phototoxicity and shallow tissue penetration. However, their insufficient LW light absorption and low singlet oxygen quantum yield (Φ 1O2) usually require high laser power density to produce thermal energy and synergistically enhance PDT. The strong photothermal radiation causing acute pain significantly reduces patient compliance and hinders the broader clinical application of LW PDT. Through the exciton dynamics dissection strategy, we have developed a series of pH-activatable cyanine-based LW PSs (LET-R, R = H, Cl, Br, I), among which the activated LET-I exhibits strong light absorption at 808 nm and a remarkable 3.2-fold enhancement in Φ 1O2 compared to indocyanine green. Transient spectroscopic analysis and theoretical calculations confirmed its significantly promoted intersystem crossing and simultaneously enhanced LW fluorescence emission characteristics. These features enable the activatable fluorescence and photoacoustic dual-modal imaging-escorted complete photodynamic eradication of tumors by the folic acid (FA)-modified LET-I probe (LET-I-FA), under the ultralow 808 nm laser power density (0.2 W cm-2) for irradiation, without the need for photothermal energy synergy. This research presents a novel strategy of dissecting exciton dynamics to screen activatable LW PSs for traceable PDT.

Exploring the impact of meso-position fluorination on BODIPYs: Synthesis, electrochemical Insights, and potential therapeutic applications in breast cancer

Three boron dipyrromethane molecules (BODIPYs) were synthesized in this study with different quantities of fluorine in the meso position. The samples were characterized by NMR spectroscopy, absorption, mass spectrometry, and cyclic voltammetry, which was utilized to electrochemically measure the energy gaps between the HOMO (highest-energy occupied molecular orbital) and LUMO (lowest-energy unoccupied molecular orbital). The MTT and SRB assays were used to assess the viability of these dyes in breast cancer cells (MCF-7 and HCC-1806) and African green monkey kidney cells (Vero). The newly synthesized BODIPY tris(perfluorophenoxy)phenyl (1) compound has exhibited remarkable stability and lacks photocytotoxicity in this investigation, thus rendering it a promising candidate for application in bioimaging. At defined concentrations, the BODIPYs bearing perfluorophenyl (2) and hydroxyphenyl (3) moieties have been identified as prospective candidates for photosensitization in photodynamic therapy for breast cancer. Their notable phototoxic properties upon irradiation and the absence of significant metabolic activity reduction in normal VERO cells after 24 h of exposure suggest their potential efficacy in this therapeutic approach.

Thio and Seleno-Psoralens as Efficient Triplet Harvesting Photosensitizers for Photodynamic Therapy.

The Psoralen (Pso) molecule finds extensive applications in photo-chemotherapy, courtesy of its triplet state forming ability. Sulfur and selenium replacement of exocyclic carbonyl oxygen of organic chromophores foster efficient triplet harvesting with near unity triplet quantum yield. These triplet-forming photosensitizers are useful in Photodynamic Therapy (PDT) applications for selective apoptosis of cancer cells. In this work, we have critically assessed the effect of the sulfur and selenium substitution at the exocyclic carbonyl (TPso and SePso, respectively) and endocyclic oxygen positions of Psoralen. It resulted in a significant redshifted absorption spectrum to access the PDT therapeutic window with increased oscillator strength. The reduction in singlet-triplet energy gap and enhancement in the spin-orbit coupling values increase the number of intersystem crossing (ISC) pathways to the triplet manifold, which shortens the ISC lifetime from 10-5 s for Pso to 10-8 s for TPso and 10-9 s for SePso. The intramolecular photo-induced electron transfer process, a competitive pathway to ISC, is also considerably curbed by exocyclic functionalizations. In addition, a maximum of 115 GM of two-photon absorption (2PA) with IR absorption (660-1050 nm) confirms that the Psoralen skeleton can be effectively tweaked via single chalcogen atom replacement to design a suitable PDT photosensitizer.

Overcoming melanin interference in melanocyte photodynamic therapy with a pyrene-derived two-photon photosensitizer

Photodynamic therapy (PDT) is primarily applied in the treatment of skin diseases. However, conventional PDT is less effective for melanoma, a type of skin cancer that contains melanin pigment, due to melanin’s broad absorption spectrum in the ultraviolet–visible region. This reduces the effectiveness of traditional photosensitizers (PSs) in PDT. Here, we introduced pyrene based two-photon (TP) PSs that are easy to synthesize. Among the π-extended pyrene derivatives, we have confirmed the synergetic generation of reactive oxygen species (ROS) with asymmetric pyrene (Py3). We proposed a mechanism explaining the higher ROS generation efficiency of Py3 compared with that of the symmetric derivatives through theoretical calculations. Py3 effectively stains the plasma membrane of melanoma cells and demonstrates superior PDT efficacy compared with Chlorin e6. As the melanin content increases in melanoma cells, cell death significantly decreases under visible light excitation; notably, it is minimally affected by TP irradiation at 750 nm. In 3D multicellular tumor spheroids with a high melanin content, Py3 showed high PDT efficacy through TP irradiation, whereas under visible light irradiation, PDT efficacy decreased. In experiments involving the injection of Py3 into the tail of mice with B16F10 and 4 T1 tumor models, followed by TP-PDT, we observed significant inhibition of tumor growth and high biocompatibility. Our results indicate a promising TP-PDT method for treating melanomas.

The Multifaceted Actions of PVP-Curcumin for Treating Infections.

Curcumin is a natural compound that is considered safe and may have potential health benefits; however, its poor stability and water insolubility limit its therapeutic applications. Different strategies aim to increase its water solubility. Here, we tested the compound PVP-curcumin as a photosensitizer for antimicrobial photodynamic therapy (aPDT) as well as its potential to act as an adjuvant in antibiotic drug therapy. Gram-negative E. coli K12 and Gram-positive S. capitis were subjected to aPDT using various PVP-curcumin concentrations (1-200 µg/mL) and 475 nm blue light (7.5-45 J/cm2). Additionally, results were compared to aPDT using 415 nm blue light. Gene expression of recA and umuC were analyzed via RT-qPCR to assess effects on the bacterial SOS response. Further, the potentiation of Ciprofloxacin by PVP-curcumin was investigated, as well as its potential to prevent the emergence of antibiotic resistance. Both bacterial strains were efficiently reduced when irradiated with 415 nm blue light (2.2 J/cm2) and 10 µg/mL curcumin. Using 475 nm blue light, bacterial reduction followed a biphasic effect with higher efficacy in S. capitis compared to E. coli K12. PVP-curcumin decreased recA expression but had limited effect regarding enhancing antibiotic treatment or impeding resistance development. PVP-curcumin demonstrated effectiveness as a photosensitizer against both Gram-positive and Gram-negative bacteria but did not modulate the bacterial SOS response.