Microbial contamination remains a critical concern in water and biomedical contexts, motivating the search for sustainable disinfection strategies that minimize chemical inputs and energy demand. Blue light (400-470 nm) can inactivate bacteria via endogenous porphyrin photoactivation and reactive oxygen species (ROS) generation; however, significant antimicrobial effects typically require high fluences (>100 J cm-2), particularly at longer wavelengths such as 470 nm, limiting practical applications. Therefore, strategies that lower the required dose without introducing exogenous photosensitizers are highly desirable. Here, we investigate the previously reported vanillin-derived polyimine (VP) as a photo-inert interfacial modulator of bacterial susceptibility to blue light. Although VP is not itself a photosensitizer, it enhances blue-light antibacterial efficacy against Staphylococcus aureus by inducing sublethal stress that increases susceptibility to endogenous photo-oxidative pathways. VP films alone did not reduce bacterial viability after 90 min of dark incubation, but colony morphology, growth kinetics, and scanning electron microscopy revealed the induction of sublethal cellular stress. When combined with 470 nm irradiation at moderate fluences (18-54 J cm-2), selected to provide a weak light-only antibacterial action to reveal possible VP-mediated priming effects, VP films exhibited a reuse-dependent enhancement of antibacterial activity, with limited effect at first use and progressively stronger killing upon repeated reuse, ultimately approaching a 2-log reduction. Structural analyses (BET/BJH) showed that reuse-induced micro fracturing increased the specific surface area (12.9 m2 g-1 for pristine films vs. 21.8 m2 g-1 after reuse) without altering pore size distribution, thereby enhancing polymer-cell interactions. Importantly, no measurable generation of singlet oxygen, radical species, or hydrogen peroxide by the polymer was detected under the tested conditions, indicating that antibacterial activity arises from polymer-mediated sensitization of bacterial endogenous photo-oxidative pathways. Overall, these results support a priming-plus-light mechanism, in which a neutral polyimine induces sublethal physiological stress that amplifies bacterial susceptibility to blue-light irradiation under deliberately mild irradiation conditions.
Rare earth nanoparticles (RENPs) have emerged as promising nanoplatforms for photodynamic therapy (PDT) owing to their optical conversion capability, tunable emission, imaging compatibility, and surface-engineering flexibility. RENPs can convert deeply penetrating near-infrared (NIR) light or high-energy radiation into emissions that activate photosensitizers (PSs), thereby improving light delivery, reactive oxygen species (ROS) generation, and spatiotemporal therapeutic control. This review summarizes recent advances in RENP-mediated PDT, focusing on photosensitizer activation, tumor targeting, regulated cell death, and ROS amplification. We also discuss RENP-based theranostic and multimodal therapeutic platforms that combine imaging guidance with photothermal therapy (PTT), chemotherapy, immunotherapy, gene regulation, and tumor microenvironment (TME) modulation. Finally, we critically analyze the major translational barriers, including limited optical conversion efficiency under clinically acceptable power densities, excitation-induced heating, tumor hypoxia, antioxidant defense, scalable manufacturing, long-term biosafety, and patient stratification. Future development should prioritize simplified material design, standardized quality control, low-power excitation, reliable safety evaluation, and indication-specific clinical positioning.
The photoinduced hemolysis of erythrocytes mediated by porphyrin photosensitizers - the anionic 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS4), cationic 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP), and their respective zinc (II) complexes (ZnTPPS₄ and ZnTMPyP) - was evaluated spectrophotometrically by monitoring hemoglobin release and malondialdehyde (MDA) formation. Erythrocyte ghosts (EG) were used as a model to evaluate the photohemolysis, which proved to be caused by photodecomposition of erythrocyte membrane due to lipid peroxidation. The photohemolytic efficiency of the porphyrins increases in the sequence TPPS4 < ZnTPPS4 < TMPyP < ZnTMPyP which coincides with the porphyrin affinity to the erythrocyte membrane, determined by fluorescence spectroscopy methods. Using the EPR spin trap method, it was shown that lipid peroxidation of EG is performed through the generation of both radical reactive oxygen species (ROS) (Type I mechanism) and singlet oxygen (Type II mechanism); however, it should be noted that the detected ROS predominantly originate in the surrounding solution rather than exclusively at the membrane interface, although they contribute to membrane lipid peroxidation. The highest photodynamic activity of ZnTMPyP is due to both its highest affinity for EG membranes and highest quantum yield of the excited triplet state formation, which is responsible for the efficient production of both singlet oxygen and radical ROS species.
Light is both the primary energy source for photosynthesis and a key regulator for circadian rhythms, influencing the comprehensive quality and the production cycle of plants. Light quality is a critical parameter of light parameters, and the response patterns of photosynthesis and circadian rhythm to different light qualities remain to be explored. Here, white (broad-spectrum), red, blue and purple lights were each applied to celery for two days (light/dark: 12 h/12 h), and stomatal openness, photosynthetic parameters, photosynthetic pigments contents, and the expression levels of photoreceptor-related genes were measured. The results showed, narrow-spectrum treatments outperformed white light in both photosynthetic parameters and pigments accumulation red light most effectively promoted stomatal openness and net photosynthetic rate (Pn), reached the maximum levels after 4 h of illumination. Compared with white light, the average contents of photosynthetic pigments were improved 1.12, 1.25 and 1.37 times higher under the red, blue, and purple light, respectively. Furthermore, within the two days, narrow-spectrum treatments upregulated the maximal relative expression of most photoreceptor genes (especially AgPHYB and AgPHOT2). The expression of circadian rhythm genes previously established under white light were disrupted, leading to disordered expression, complex uncoupling or loss of rhythmicity. This research provided references for light quality response mechanism researches and facility-based light supplementation in celery cultivation.
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with high resistance and recurrence rate. Here we present a novel combination therapy composed of Selinexor, a selective nuclear export (XPO1) inhibitor, and 5-aminolevulinic acid (5-ALA), a protoporphyrin IX (PpIX) precursor. Selected drugs act through two distinct mechanisms of action: Selinexor retains tumor suppressor proteins within the nucleus, while 5-ALA, after being converted to PpIX, induces oxidative stress upon light exposure. Intracellular accumulation of PpIX in U-87 MG cells peaked at 4 h and co-administration of the drugs to U-87 MG cells yielded strong synergism with substantially reduced doses of 5-ALA and Selinexor up to ∼140- and ∼ 29-fold, respectively. Conversely, very strong antagonism was observed in the control cell line. While the highest mitochondrial H₂O₂ production was measured following 5-ALA induced photodynamic therapy (PDT), Selinexor reduced H₂O₂ level. The strong synergistic interaction between the two drugs enhanced therapeutic outcome by suppressing cell migration and inducing apoptosis with markedly lower drug doses. These findings suggest that the combination therapy of Selinexor and 5-ALA/PDT may increase the chances of successful GBM treatment compared to monotherapy alone.
Diabetic kidney injury, a severe complication of diabetes, involves complex pathological mechanisms where the role of hydroxyl radicals (•OH) remains insufficiently explored due to the lack of suitable detection tools. To address this gap, a hydroxyl radical-activated near-infrared photoacoustic probe, OHSO3, was developed. In vitro validation confirmed its high sensitivity, excellent selectivity, and low cytotoxicity. Leveraging sulfonate group-enhanced hydrophilicity for favorable renal clearance, OHSO3 enabled non-invasive, real-time imaging of renal •OH in a diabetic mouse model. The probe successfully visualized elevated •OH levels in injured kidneys and quantitatively monitored their attenuation following metformin treatment. This study provides not only a reliable molecular tool for •OH-specific imaging but also a promising strategy for studying oxidative dynamics and evaluating therapies in diabetic nephropathy.
Resistance to anti-epidermal growth factor receptor (EGFR) antibodies represents a major bottleneck in treating EGFR-overexpressing tumors such as skin cancer. While conventional photodynamic therapy offers a promising alternative, its efficacy is often constrained by poor targeting and limited tissue penetration. To address this, we developed a photoimmunodiagnostic-therapeutic conjugate (PPC) based on panitumumab and the near-infrared photosensitizer IR808, aiming to integrate tumor-specific targeting, real-time fluorescence imaging, and synergistic therapy. In vivo experiments demonstrated that PPC selectively accumulates at tumor sites, enabling sustained near-infrared fluorescence imaging. Following light exposure, it significantly suppressed tumor growth through the synergistic effects of photodynamic killing and immune activation without inducing notable systemic toxicity. This study offers a novel integrated diagnostic-therapeutic strategy for EGFR-positive malignancies, highlighting the photobiological mechanisms underlying its antitumor effects and demonstrating the potential of antibody-photosensitizer conjugates in photomedicine.
The tumor microenvironment (TME), characterised by immunosuppression, hypoxia, acidity, and high interstitial pressure, creates a unique microenvironment that facilitates tumorigenesis and treatment resistance. Photodynamic therapy (PDT) has emerged as a promising and effective modality for cancer treatment. Beyond the intrinsic parameters of PDT, increasing evidence indicates that the TME critically regulates therapeutic efficacy and contributes to the development of acquired resistance. Targeted modulation of the TME to enhance PDT outcomes and overcome resistance has therefore become an attractive therapeutic strategy. This review systematically summarizes the effects of key TME characteristics-including acidic conditions, immunosuppressive states, hypoxia, and elevated interstitial fluid pressure on PDT efficacy and the mechanisms underlying PDT-acquired resistance. Furthermore, current combination strategies aimed at remodeling the TME to improve PDT performance are comprehensively discussed, with particular emphasis on biomaterial-based therapeutic approaches. Finally, in view of the limitations of existing combination therapies, future research directions are highlighted, focusing on a deeper understanding of the dynamic evolution of the TME and the development of intelligent nanomaterial-based targeted delivery platforms to enable precise and personalized PDT.
The growing demand for alternative cancer treatments has intensified interest in photodynamic therapy (PDT), a minimally invasive approach that combines light irradiation with photosensitizing agents (PSs) to achieve localized cytotoxicity. Phenothiazine derivatives are well established as antimicrobial and anticancer PSs, positioning 1,9-dimethyl methylene blue (DMMB) as a promising candidate. However, the photodynamic performance of DMMB against oropharyngeal carcinoma, particularly as a function of photosensitizer concentration and light dose, remains poorly explored. Here, we investigate the molecular interactions and photodynamic effects of DMMB using membrane-mimetic systems based on lipid extracts from human oropharyngeal carcinoma cells (HEp-2), complemented by in vitro cellular assays. Langmuir monolayers revealed strong membrane affinity of DMMB, leading to pronounced monolayer expansion (up to ∼90% at 1.0 μmol/L) and changes in elastic properties. Upon photoactivation, DMMB induced concentration- and light dose-dependent reductions in monolayer surface area, consistent with light-triggered photodynamic effects at the membrane interface. At 0.1 μmol/L, a modest decrease of ∼3.5% was observed, whereas at 1.0 μmol/L the surface area reduction increased from 6.9% to 13.4% as the light dose rose from 1 to 18 J/cm2. FTIR spectroscopy of Langmuir-Schaefer films revealed limited spectral changes mainly associated with interfacial lipid regions, particularly carbonyl hydration and relative intensity variations, while phosphate and acyl-chain regions were largely preserved. Cellular assays were consistent with the interfacial findings. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) assays demonstrated pronounced phototoxicity in HEp-2 cells with no detectable dark toxicity, yielding IC₅₀ values that decreased from 0.82 μmol/L at 1 J/cm2 to 0.35 μmol/L at 18 J/cm2. Increased LDH release and confocal fluorescence microscopy revealed plasma membrane disruption and intracellular damage consistent with light-induced membrane perturbation inferred from the monolayer studies, which may involve lipid oxidation-related processes. Overall, these results support an association between DMMB-membrane interactions and cellular phototoxicity, highlighting how photosensitizer concentration and light dose modulate DMMB photodynamic effects under the investigated experimental conditions. DMMB thus emerges as a promising candidate for further investigation in oropharyngeal carcinoma PDT models.
Photodynamic therapy (PDT) has emerged as a promising modality for cancer treatment; however, the clinical translation of many photosensitizers remains limited by poor aqueous solubility, unfavorable biodistribution, and insufficient tumor accumulation. In this study, we investigated whether PEGylation of the photosensitizer Photomed could improve its physicochemical properties and in vivo photodynamic therapeutic efficacy without compromising its intrinsic photochemical activity. A PEG-conjugated Photomed (Photomed-PEG) was synthesized and systematically evaluated using singlet oxygen generation assays, cellular uptake studies, and in vitro phototoxicity assessments. In vivo biodistribution and antitumor efficacy were further examined in an A549 tumor-bearing mouse model. PEGylation markedly enhanced the aqueous solubility of Photomed while preserving efficient singlet oxygen generation and minimal dark toxicity. Moreover, Photomed-PEG exhibited enhanced tumor accumulation with reduced off-target retention compared to its non-PEGylated counterpart. These favorable pharmacokinetic properties translated into significantly improved photodynamic antitumor efficacy, as evidenced by pronounced tumor growth suppression following PDT. Importantly, no significant body weight loss or histopathological abnormalities in major organs were observed, indicating an acceptable safety profile. Collectively, these findings demonstrate that PEGylation represents an effective strategy for optimizing photosensitizer delivery and enhancing in vivo therapeutic performance for solid tumors.
Paclitaxel (PTX), a potent chemotherapeutic agent, faces significant clinical limitations due to poor aqueous solubility, systemic toxicity, and non-specific biodistribution, particularly in advanced peritoneal metastases. To overcome these challenges, we developed a carrier-free, self-assembled theranostic nanoprodrug system, IPSP NPs, integrating a thioketal-bridged paclitaxel dimer (PSP) with the near-infrared (NIR) fluorophore IR783. This innovative design enables reactive oxygen species (ROS)-responsive drug release and simultaneous NIR imaging. Comprehensive characterization confirmed the formation of stable, monodisperse IPSP NPs (∼161 nm) with high encapsulation efficiencies for both PSP (∼72.4%) and IR783 (∼89.4%). In vitro studies demonstrated robust ROS-triggered PTX release from IPSP NPs and a "prodrug latency effect" in colon cancer cells, showcasing stability at low concentrations and high cytotoxicity at therapeutic levels. In vivo evaluations in a CT26-Luc1 murine peritoneal metastasis model revealed favorable biodistribution with sustained tumor accumulation and significant tumor suppression comparable to free PTX. Histopathological analysis (H&E, Ki-67, TUNEL) demonstrated profound tumor cell damage, induced apoptosis, and inhibited proliferation by IPSP NPs. Crucially, IPSP NPs exhibited superior biosafety profiles, evidenced by normal organ histologies and improved renal function (reduced uric acid levels) compared to free PTX, highlighting reduced off-target toxicity. This work establishes a promising strategy for polymer-free theranostic nanoparticles, offering enhanced tumor targeting, controlled drug release, imaging capabilities, and improved safety for cancer therapy.
Prolonged light exposure is an important environmental risk factor for retinal degeneration, yet the interaction between distinct cell death pathways during retinal photodamage remains unclear. Here, we demonstrate that light injury simultaneously activates PARP-1-dependent parthanatos and PINK1/Parkin-mediated mitophagy in photoreceptor cells. Light exposure markedly increased PARP-1 activity, poly(ADP-ribose) (PAR) accumulation, and mitophagy-related proteins, including PINK1, p-Parkin, and LC3B-II. Importantly, our results reveal a previously unrecognized crosstalk between parthanatos and mitophagy. PARP-1 inhibition not only attenuated parthanatos but also suppressed excessive mitophagy, indicating that PARP-1 acts as a key upstream regulator linking these two pathways. Conversely, inhibition of mitophagy alleviated light-induced retinal damage. Both in vitro and in vivo experiments further demonstrated that combined inhibition of PARP-1 and mitophagy produced a stronger neuroprotective effect than either intervention alone, preserving photoreceptor structure and retinal function. These findings identify PARP-1-mediated crosstalk between parthanatos and mitophagy as a critical mechanism underlying retinal light injury and provide a potential therapeutic strategy for photoreceptor degeneration.
Fluorescence lifetime imaging microscopy (FLIM) using endogenous fluorescence of NADH (reduced nicotinamide adenine dinucleotide) and its phosphorylated form NADPH represents a powerful tool for monitoring cellular metabolic states. For a more nuanced interpretation of the FLIM data, investigating NAD(P)H in different cell compartments is crucial. In this study, we demonstrate that a weak NAD(P)H fluorescence in cell nuclei, which is often ignored, can be reliably analyzed using a phasor plot approach and provides a sensitive readout of metabolic responses. Using colorectal cancer cells HCT116 treated with the metabolic inhibitors rotenone and 3-bromopyruvate, as well as the chemotherapeutic agent 5-fluorouracil (5-FU), we show that nuclear NAD(P)H fluorescence decay changes in response to treatment. In the case of 5-FU, the phasor analysis of nuclear NAD(P)H reveals heterogeneous cellular responses with two subpopulations differing in NAD(P)H fluorescence decay parameters, fluorescence intensity, and cytoplasm-to-nucleus intensity ratio. Notably, nuclear and cytoplasmic responses are strongly correlated, indicating tight coupling of their NAD(P)H pools. Overall, our results establish nuclear NAD(P)H fluorescence as a robust, label-free indicator of cellular metabolism and highlight its potential for metabolic monitoring in conditions where analysis of NAD(P)H fluorescence is limited by spectral overlap with exogenous fluorescent labels.
Elucidating the fundamental interrelation between hydrogen peroxide (H2O2)/viscosity and mitochondria related diseases still is a major issue due to the lack of an excellent tool for long-term tracking of mitochondrial viscosity and hydrogen peroxide. Herein, we devised an MMP-independent probe, BKI, which could simultaneously detect fluctuations of viscosity and H2O2. BKI shows a good response to H2O2 with a low detection limit of 34 nM, mediated by the specific reaction between H2O2 and the borate ester moiety. Moreover, BKI can also monitor the viscosity fluctuations with green emission at 475 nm due to the rotation of its vinyl double bond. Notably, BKI not only localizes in mitochondria accurately but also firmly immobilizes in mitochondrial inner membrane through hydrophobic interactions between its long alkyl chains and lipids on the mitochondrial membrane, enabling long-term monitoring mitochondrial viscosity and H2O2. Using BKI, the viscosity changes induced by monensin or nystatin, as well as exogenous and endogenous H2O2 in living cell were successfully visualized. In particular, the unique probe can distinguish between normal tissues and tumor tissues of cancer patients by detecting viscosity and H2O2. These results imply that BKI can be served as a powerful tool for long-term visualizing mitochondrial viscosity and H2O2 in vitro and in vivo.
Bioluminescence, generated through the luciferase-catalyzed oxidation of luciferin, produces visible light and is widely used in biomedical imaging and related fields. Imidazopyridine (ImPy) constitutes the core luminescent scaffold of coelenterazine-type fluorophores, and its oxidation yields an anionic dioxetanone intermediate that typically undergoes cleavage. This process generally involves charge transfer between substituents and the formation of radical electrons, a phenomenon known as charge-transfer-induced luminescence (CTIL). The anionic dioxetanone can also be converted to its neutral form through protonation or intramolecular bonding. Although neutral dioxetanone can likewise undergo cleavage accompanied by charge transfer between substituents, the transferred charge is small. It has therefore often been overlooked, leading to the prevailing assumption that neutral-state cleavage does not belong to the CTIL category. The mechanistic distinction between these two cleavage modes remains unresolved. In this work, an ImPy model was constructed based on the structures of coelenterazine and furimazine, two representative marine luciferins. Using density functional theory (DFT), we computed the oxidation pathway leading to dioxetanone formation and examined its cleavage under various anionic and neutral states. Charge-transfer behavior and reaction barriers were evaluated, and wavefunction analyses were performed to visualize the evolution of radical-electron distribution and atomic interactions throughout the reaction. Our results show that although the amount of charge transferred between substituents in the neutral state is small, it remains essential, as these subtle charge shifts initiate dioxetanone cleavage. Neutral-state cleavage should therefore be classified as part of the CTIL mechanism, consistent with the anionic case. In both neutral and anionic states, the reaction is triggered by the transfer of negative charge to the central CCOO four-membered ring, and this transferred charge induces dissociation of the two oxygens, thereby initiating dioxetanone cleavage. In the anionic state, the pyrazinamine (PMN) moiety, which carries a substantial negative charge adjacent to CCOO, acts as the donor. The donated charge initially drives the separation of the two oxygen atoms within CCOO, subsequently propagates through the dioxetanone framework, induces cleavage of the C-C bond, and ultimately results in dioxetanone dissociation. In the neutral state, the only available donor is a single carbonyl oxygen atom, and the donated negative charge is sufficient only to separate the two oxygen atoms but insufficient to cleave the C-C bond of the CCOO ring. Additional energy is therefore required to amplify charge transfer and achieve full C-C bond rupture. By varying the initial negative charge load on the donor moiety, we further identified that a higher negative charge facilitates transfer to CCOO and thereby lowers the reaction barrier.
BACKGROUND:Laser-assisted in-office bleaching has been proposed to enhance whitening efficacy by accelerating hydrogen peroxide (H₂O₂) degradation and optimizing oxidative reactions. Nevertheless, Er:YAG laser influence on thermal behavior, peroxide kinetics, optical performance, and trans-amelodentinal diffusion remains insufficiently elucidated. Thus, this in-vitro study evaluated the combined effects of Er:YAG laser activation and different H₂O₂ gel concentrations on thermal, chemical, and optical responses during enamel bleaching. METHODS:186 bovine incisors were allocated into six groups according to H₂O₂ concentration (9%, 17.5%, and 35%) and Er:YAG irradiation (with or without activation). Phase I assessed temperature at the enamel surface and pulp chamber, and H₂O₂ degradation at distinct evaluation periods. Phase II evaluated chromatic alteration (ΔE00), whitening index (WID) in relation to established perceptibility and acceptability thresholds, and trans-amelodentinal diffusion of H₂O₂. Statistical analyses were performed using ANOVA followed by Tukey post hoc tests (α = 0.05). RESULTS:Higher H₂O₂ concentrations resulted in significantly greater ΔE00 and WID values; however, these effects were accompanied by increased temperature and peroxide diffusion. Notably, comparisons between the highest and lowest H₂O₂ gel concentrations, irrespective of laser irradiation, exceeded the established whitening perceptibility threshold. Er:YAG irradiation significantly accelerated H₂O₂ degradation and enhanced whitening outcomes compared with non-irradiated groups. Notably, laser activation reduced trans-amelodentinal peroxide diffusion across all evaluated H₂O₂ gel concentrations. Overall, reductions in temperature and H₂O₂ gel concentration were observed over time. CONCLUSIONS:Er:YAG-assisted bleaching modulates peroxide degradation kinetics, enhances whitening efficacy, and influences thermal and trans-amelodentinal peroxide diffusion.
Periodontitis is a chronic biofilm-induced inflammatory disease that is increasingly linked to systemic conditions. Effective treatment requires removing pathogenic biofilms and modulating the host inflammatory response. Antibacterial photodynamic therapy (aPDT) shows promising potential in the field of antibacterial treatment. However, issues such as the hypoxic microenvironment within periodontal pockets and biofilm structures, as well as the poor stability of traditional photosensitizers, pose challenges to the efficacy of aPDT. Here, we developed a multifunctional nanoparticle MB-MnO₂@PLGA NPs (MMP NPs) by co-encapsulating methylene blue (MB) and PVA-pre-dispersed manganese dioxide (MnO₂) nanosheets into a PLGA nanocarrier using a double emulsion-solvent evaporation method. Characterization confirmed their core-shell morphology, good colloidal stability, and high MB loading. Upon 660 nm irradiation, the nanoparticles generated reactive oxygen species and catalyzed H₂O₂ to produce oxygen, relieving local hypoxia and enhancing the cell compatibility of free MB. The MMP NPs disrupted P. gingivalis and F. nucleatum biofilms and exhibited superior antibacterial activity compared to free MB. Additionally, the nanoplatform significantly downregulated IL-6 and TNF-α levels. Importantly, the nanoplatform promoted macrophage polarization toward an anti-inflammatory M2 phenotype, as indicated by increased Arg-1 and CD206 expression. This work supports a synergistic in vitro strategy that simultaneously targets infection, hypoxia, and inflammation. It holds positive significance for promoting the development of periodontal disease treatment.
Alternative anticancer therapies are gaining momentum in modern medicinal chemistry and photodynamic therapy (PDT) is one of the most studied nowadays. In this paper we explore the biological features of unique photosensitiser (PS) - hydrolytically stable CC bonded glycoporphyrin (PS 1). The glycoconjugate has been obtained via modified Sonogashira reaction protocol under microwave irradiation. Glycosylation of the porphyrin system allowed to significantly reduce its dark cytotoxicity while such modification still did not hamper production of reactive oxygen species (ROS) after light irradiation. The phototherapeutic activity of PS 1 was compared with the activity of PS 2, example of unmodified synthetic porphyrin. Herein, we present chemical and biological experiments presenting effectiveness of these compounds in ROS production, cellular uptake studies, and evaluation of glycoporphyrin utility in PDT. The absence of measurable dark cytotoxicity across all examined cell lines within the tested concentration range (2.5-100 μM), combined with a clear light-induced effect, indicates a favourable selectivity profile of PS 1 at the in vitro screening stage.
A combination of rapid disease progression and insufficient therapeutic options continues to complicate the clinical management of anaplastic thyroid carcinoma (ATC). The antitumor effect of photothermal therapy (PTT) arises from heat generated in situ, leading to tumor cell damage. However, its therapeutic efficacy is constrained by insufficient tissue penetration and inadequate immune activation, making complete tumor eradication challenging. Despite its ability to induce antitumor immune responses, CpG oligodeoxynucleotide (CpG ODN)-mediated immunotherapy shows limited efficacy as a standalone approach and does not sufficiently improve the immunosuppressive conditions within the tumor microenvironment. Photothermal therapy (PTT), when used alongside CpG ODN-mediated immunotherapy, may provide enhanced antitumor effects arising from their complementary functions. In this study, we developed a nanoplatform integrating CpG ODN-mediated immune activation with the photothermal properties of Fe3+-doped polydopamine for the treatment of ATC. Assessment of the nanoplatform revealed satisfactory compatibility in biological contexts, accompanied by reproducible photothermal conversion performance. In vitro assessment revealed enhanced dendritic cell maturation, accompanied by an increase in pro-inflammatory cytokine production following this treatment. The combined treatment, when evaluated in vivo, was linked to decreased tumor growth and coincided with immunogenic cell death, increased dendritic cell maturation, enhanced T cell infiltration, and alterations in the immunosuppressive tumor microenvironment. Use of the combinational strategy resulted in greater antitumor effects than monotherapies, accompanied by direct tumor ablation and the activation of systemic immune responses. A therapeutic benefit for ATC may be achieved through the integration of photothermal therapy with immunotherapy.
Blue light, also known as high energy visible (HEV) light, is the most energetic light reaching the adult retina. HEV light exerts its toxicity mainly through chromophore photosensitization reactions. Some components found in atmospheric pollution can absorb light and act as exogenous chromophores. This study aims to assess the impact of the co-exposure to HEV light and wood combustion smoke extract, on retinal pigment epithelium (RPE) cells. We show that these two factors act in synergy causing RPE cell viability loss. Co-exposure to HEV light and wood smoke extract leads to oxidative stress that can be mitigated by antioxidant. This indicates the presence of HEV light-sensitive chromophore(s) amongst the wood smoke components. In response to the oxidative stress induced by wood smoke and HEV light, RPE cells activate the detoxification pathway nuclear factor erythroid 2-related factor 2 (Nrf2). Our results bring the first evidence that co-exposure to smoke from wood combustion and light is toxic for human retina.
