Search Results (342)

Photodynamic therapy (PDT) combines a photosensitizer (PS), light, and molecular oxygen to generate cytotoxic reactive species, but nominally similar regimens can produce different biological responses because prescribed inputs do not directly specify the biologically active exposure state. Here, this intermediate state is treated as a multidimensional profile defined by PS localization and photoactive availability, the intratissue light field, oxygen dynamics, and vascular conditions at illumination. The relative contributions of direct tumor-cell injury, vascular damage, inflammatory signaling, and adaptive immune modulation also depend on drug–light interval (DLI), treatment sequence, vascular architecture, and tumor–host context. This critical narrative review applies a parameter–exposure state–mechanism–endpoint framework to oncologic PDT. It distinguishes spatially restricted primary photochemical injury from downstream multicellular effects and appraises the evidentiary thresholds for immunogenic cell death (ICD) and systemic immune claims. It also proposes reporting considerations and translational priorities to improve study comparability. PDT mechanisms should be interpreted against measurable treatment parameters rather than presumed from a PS label or prescribed dose alone. Full article

Background: Photodynamic therapy (PDT) is a cancer treatment that combines a photosensitizer (PS), light, and oxygen to generate reactive oxygen species (ROS), leading to tumor cell death. PDT efficacy depends largely on PS accumulation within tumors, prompting the development of third-generation PSs and nanotechnology-based delivery systems. Among these, BODIPYs (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) are promising PSs due to their favorable photophysical properties, while liposomes improve drug delivery, cellular uptake, and sustained release profiles. This study describes the synthesis of two novel BODIPY derivatives differing in the position of a methyl ester group on the meso-phenyl ring, their incorporation into liposomes, and evaluation of PDT efficacy. Methods: Cellular uptake of BODIPY-loaded liposomes, intracellular ROS generation, apoptosis, necrosis, and lipid peroxidation were assessed by flow cytometry in colorectal and ovarian cancer cell lines. The antitumor activity of the liposomal formulations was further evaluated in both 2D and 3D models using MTT and clonogenic assays. The involvement of ferroptosis and necroptosis in PDT-induced cell death was also investigated. Results: Liposomal formulations significantly enhanced cellular uptake compared with free compounds. Following light activation, both formulations induced potent antitumor effects through multiple cell death mechanisms, including canonical and non-canonical pathways, and maintained strong efficacy in 3D tumor spheroids. Conclusions: Liposome-encapsulated BODIPYs represent promising PDT agents by improving cellular uptake and eliciting robust antitumor activity through complementary cell death mechanisms. Furthermore, the methyl ester substituent on the meso-phenyl ring provides a versatile platform for future conjugation with targeting ligands, supporting the development of third-generation, tumor-targeted photosensitizers and warranting further preclinical investigation. Full article

Background: Antimicrobial resistance represents a growing global health challenge, necessitating the development of effective non-antibiotic antimicrobial approaches. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising localized antimicrobial strategy owing to its broad-spectrum activity, biofilm-targeting capability, and low propensity to induce resistance. However, its clinical translation remains restricted by limited photosensitizer (PS) performance, insufficient light penetration, oxygen dependency, biofilm-associated barriers, and the lack of standardized treatment protocols. Methods: This narrative review summarizes recent strategies developed to enhance the efficacy and translational potential of aPDT, including PS engineering, nanomaterial- and non-nanomaterial-based delivery systems, advanced light-source technologies, hypoxia-modulating approaches, and synergistic therapeutic strategies. In addition, current challenges associated with regulatory approval, manufacturing scalability, treatment standardization, and clinical implementation are discussed. Results: Recent advances have transformed aPDT from a conventional PS–light–oxygen system into a multifunctional antimicrobial platform. Emerging approaches improve bacterial targeting, biofilm penetration, reactive oxygen species generation, oxygen utilization, and therapeutic precision. Nevertheless, many advanced systems remain at the preclinical stage due to complexity, cost, safety concerns, and insufficient clinical validation. Conclusions: aPDT should be considered a targeted therapeutic option for accessible, localized, and biofilm-associated infections rather than a replacement for systemic antimicrobial therapy. Future clinical translation will depend on balancing technological innovation with biosafety, scalability, and protocol standardization. Strategies integrating intelligent PS design, oxygen regulation, and clinically feasible synergistic approaches may provide promising pathways toward the broader application of aPDT in antimicrobial management. Full article

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality based on the interaction between a photosensitizer (PS), light, and molecular oxygen to generate reactive oxygen species (ROS) capable of inducing localized cytotoxicity. Natural products provide a chemically diverse source of photosensitizers, including curcumin, hypericin, hypocrellin, chlorin derivatives, alkaloids, flavonoids, anthraquinones, and other photoactive scaffolds. However, their translational development remains limited by poor solubility, aggregation, instability, variable purity, limited tissue penetration, suboptimal pharmacokinetics, and insufficient formulation readiness. In parallel, artificial intelligence (AI), including machine learning (ML), deep learning (DL), quantitative structure–activity relationship (QSAR) and quantitative structure–property relationship (QSPR) modeling, radiomics, and predictive analytics, is increasingly being applied to photosensitizer discovery, molecular property prediction, nanoformulation optimization, treatment planning, and precision PDT. This critical review evaluates the intersection between AI, natural photosensitizers, nanopharmaceutical development, and PDT, with emphasis on methodological strengths, current limitations, and translational priorities. A PRISMA 2020-inspired search strategy identified 27 studies for qualitative synthesis, comprising 11 review articles and 16 original investigations, while additional seminal references were used for historical and mechanistic contextualization. The analysis indicates that current AI applications in PDT are concentrated around molecular property prediction, QSAR/QSPR modeling, phototoxicity assessment, radiomics, image-guided therapy, and treatment-response prediction, whereas AI-guided exploration of natural photosensitizer chemical space and AI-assisted nanoformulation design remain comparatively underdeveloped. Key barriers include heterogeneous datasets, limited natural-product representation in predictive models, insufficient external validation, weak integration between formulation variables and photodynamic outcomes, and limited consideration of manufacturing and regulatory requirements. This review proposes an integrated AI-enabled translational framework connecting natural-product chemical diversity, photochemical prediction, nanocarrier optimization, precision PDT validation, and clinical implementation. Full article

Hypericin (Hyp) is a naturally occurring photosensitizer (PS) exhibiting a broad spectrum of biological activities. However, its high hydrophobicity significantly limits its medical applicability. This study aimed to develop an efficient method for extracting Hyp from Hypericum perforatum L. biomass and to obtain its water-soluble micellar formulation. A protocol for Hyp isolation from the aerial parts of the plant was established, involving a preliminary defatting step using a Soxhlet apparatus, followed by ultrasonic-assisted extraction with acetone. The water-soluble formulation was prepared via the thin-film hydration method using the nonionic block copolymer Pluronic F-127. The resulting micelles demonstrated colloidal stability, with a mean hydrodynamic diameter of approximately 30 nm. A high Hyp loading efficiency was achieved, with an encapsulation efficiency (EE) of 95.4 ± 2.7%, yielding a concentration of 600.6 ± 16.6 µM within the micellar formulation. In vitro biological studies were performed using the murine GL261 glioblastoma cell line. The micellar Hyp formulation exhibited efficient time-dependent cellular accumulation and photoinduced cytotoxicity, with no observable dark toxicity. The proposed method enables the production of a stable Hyp formulation that retains its photosensitizing properties, thereby opening promising avenues for its application in photodynamic and sonodynamic therapies. Full article

Background/Objectives: Klebsiella pneumoniae is a major pathogen involved in both acute and chronic infections, characterized by high incidence and significant clinical severity. Over the past decade, resistance to traditional antimicrobial treatments has risen rapidly, highlighting the urgent need for innovative approaches. Light-based antimicrobial strategies, including antimicrobial photodynamic therapy (aPDT), offer a promising approach for addressing drug-resistant bacteria. Combining two photosensitizers (PSs) with antibiotics synergistically enhances ROS generation and multi-target bacterial damage, achieving superior antimicrobial efficacy at reduced PS, light and antibiotic doses while limiting resistance development. We evaluated the efficacy of aPDT using the photosensitizers (PSs) methylene blue (MB) and Photodithazine (PDZ), either alone or in combination with the antibiotic ciprofloxacin (CIP), gentamicin (GEN), or ceftriaxone (CEF), against K. pneumoniae. Methods: Bacterial suspensions were treated with PDZ (25–200 µg/mL) and/or MB (5–20 µg/mL) in the presence of CIP (0.005–4 µg/mL), GEN (0.5–16 µg/mL), or CEF (0.5–16 µg/mL), followed by irradiation at either 15 J/cm² or 30 J/cm². Bacterial survival was assessed by colony-forming unit (CFU/mL) quantification. Results: The combined application of photosensitizers and antibiotics demonstrated a synergistic bactericidal effect against planktonic K. pneumoniae. The combined use of two PSs with antibiotics markedly reduced the antibiotic dose required to achieve a comparable bactericidal effect. Conclusions: This study highlights the potential of combining aPDT with conventional antibiotics as a promising strategy to combat drug-resistant infections, offering enhanced antimicrobial efficacy while allowing for reduced antibiotic dosages to achieve comparable therapeutic outcomes. Full article

Background/Objectives: Multidrug-resistant (MDR) Enterobacter spp. are critical pathogens within the ESKAPE group, frequently exhibiting resistance to carbapenems. Antimicrobial photodynamic therapy (aPDT) represents a promising non-antibiotic strategy to circumvent these resistance mechanisms. This scoping review aims to map the current evidence regarding the efficacy of aPDT in inactivating Enterobacter spp., identifying the most effective photosensitizers (PS), light parameters, and existing research gaps. Methods: A systematic search was performed across PubMed, Scopus, and Google Scholar (2013–2025) following PRISMA-ScR guidelines and registered on OSF. Studies were included if they evaluated aPDT against Enterobacter spp. (in vitro or in vivo) and provided quantitative data on microbial reduction. Data was extracted using a standardized charting form covering bacterial strains, PS type, light source, and viability reduction. The results from the eligible sources of evidence were synthesized narratively to address the review objectives. Results: Despite the clinical priority of Enterobacter, only seven studies met the eligibility criteria. Methylene Blue remains the most frequently studied PS, achieving reductions of 3–8 log₁₀. Emerging evidence highlights the synergistic efficacy of monocationic chlorins and graphene-based nanomaterials in enhancing the bactericidal effect of light-based treatments. Notably, aPDT demonstrated the ability to inactivate carbapenemases, the bacterial enzymes responsible for carbapenem resistance. However, only two studies evaluated in vivo applications, primarily within dental settings. Conclusions: aPDT is a promising method against MDR Enterobacter spp. and bypasses traditional resistance mechanisms. However, the limited number of studies indicates a significant knowledge gap. Future research should focus on standardized in vivo protocols and the synergy between aPDT and conventional antibiotics to support clinical translation. Full article

Photodynamic therapy (PDT) is a promising cancer treatment employing photo-induced reactive oxygen species (ROS) generation by a photosensitizer (PS). Titanium dioxide (TiO₂) is a potential PS due to its superb photocatalytic features and biocompatibility. However, its clinical potential is restricted by its predominant ultraviolet (UV) absorption. To address this limitation, this work introduces TiO₂/carbon dots (CDs) nanohybrid materials for improving the photophysical properties of TiO₂ and its photodynamic performance. TiO₂ and CDs were synthesized through wet chemical and hydrothermal techniques, and subsequently combined via a facile ex situ solvothermal process to produce hybrid materials containing 1–50% w/w CDs. The materials were characterized using XRD, Raman, TEM, FT-IR, zeta potential, TGA, UV-Vis and PL. PDT studies on A431 skin cancer cells indicated improved photosensitizing ability of TiO₂/CDs, with TiO₂/CDs (10%) inducing 47% cell toxicity, versus 20% for TiO₂ after 10 min of red-light irradiation (661 nm, 18 mW/cm², 12.96 J/cm²). Intracellular localization studies revealed enhanced cellular uptake of TiO₂/CDs (10%), compared with TiO₂. In vitro studies on 3T3 healthy fibroblasts confirmed PSs’ safety both with and without light. Overall, this study elucidates the key role of CDs in the photophysical and photodynamic behavior of TiO₂-based systems, providing design guidelines for the next-generation inorganic PSs. Full article

Nanotechnology combined with photodynamic therapy (PDT) has been explored to enhance antitumor and antimicrobial photobiological activity. Aluminum phthalocyanine chloride (Al-Pc-Cl), with or without magnetic nanoparticles (MagNPs), was incorporated into polymeric nanoparticles (PNPs) to improve the PDT for treating tumors and infectious diseases. Three batches of the nanoparticles (MagNPs, PNPs-PS and PNPs-PS-MagNPs) were developed and characterized in terms of size, PdI, morphology by TEM, release study, and antitumor (against A549 cells) and antimicrobial (against MRSA and C. albicans) photobiological activity. The developed nanoparticles were nanometric in size, with MagNPs, PNPs-PS, and PNPs-PS-MagNPs showing 33.6, 186.9, and 333.5 nm, respectively, maintained the magnetic properties (for MagNPs and PNPs-PS-MagNPs), and provided slow and sustained release of the photosensitizer. PNPs-PS and PNPs-PS-MagNPs showed excellent antitumor photobiological activity with cell viabilities of 42 and 34%, respectively, and were not cytotoxic in the dark, with cell viabilities above 70%. PNPs-PS showed strong antibacterial activity against MRSA with an IC₅₀ of 8.26 μg/mL, which was lower to free Al-Pc-Cl with an IC₅₀ of 14.22 μg/mL after I radiation. The results of the antifungal photobiological activity against C. albicans were excellent, with IC₅₀ values of 3.75 and 3.5 μg/mL for PNPs-PS and PNPs-PS-MagNPs, respectively, values which were significantly lower with p < 0.05 than free PS (IC₅₀ > 30 μg/mL) after irradiation with light and fluconazole (IC₅₀ > 30 μg/mL), the reference antifungal agent. PNPs-PS showed promising results regarding antitumor, antibacterial, and antifungal photobiological activity. However, PNPs-PS-MagNPs showed weak results for antibacterial photobiological activity against MRSA but with promising results for tumor cells and C. albicans. Full article

Photodynamic therapy (PDT) is a promising localized strategy for the treatment of cervical cancer, ranking as the fourth most common cancer among women worldwide. The integration of photosensitizers (PSs) in localized drug delivery systems (DDSs), particularly in electrospun nanofibers, holds tremendous potential to overcome the drawbacks of their systemic administration. Exploring multilayer fibrous architectures provides a versatile therapeutic platform to design the next generation of localized DDS. In this work, localized implants for cancer treatment using PDT were developed using polyhydroxyalkanoate (PHA), chitosan (CS) and polyethylene oxide (PEO) as biopolymers and a porphyrin (Por) as PS, following two approaches: blended PHA/Por electrospun microfibers and multilayered membranes (PHA–Por/CS/PEO) produced by sequential electrospinning. The synthesized Por displayed higher cytotoxicity in light compared to dark against tumor cells. All the developed membranes were characterized regarding their morphology, wettability, absorption and fluorescence properties. PHA–Por membranes exhibited overall uniform fibrous morphologies with successful Por incorporation. Nonetheless, they presented a highly hydrophobic surface, compromising the Por release and cell–material interactions. In contrast, multilayer PHA–Por/CS/PEO membranes demonstrated enhanced hydrophilicity and enabled sustained Por release. Upon light irradiation, these membranes induced a significantly greater inhibition of HeLa cell proliferation (29.61%) compared to dark conditions (6.21%), confirming their photodynamic activity. Full article

Breast cancer remains the most common and leading cause of cancer deaths among women worldwide. The efficacy of conventional therapies is often hampered by off-target effects and multidrug resistance. Phototherapy, encompassing photodynamic therapy (PDT) and photothermal therapy (PTT), has gained significant attention due to its non-invasiveness, high spatiotemporal selectivity, and minimal side effects. However, its application is hindered by several obstacles, including the tumor hypoxic microenvironment, insufficient light penetration depth, and acquired heat resistance. Metal–organic frameworks (MOFs) have adjustable structures, enormous specific surfaces, and facile functionalization, providing an ideal platform to overcome these limitations. This review summarizes the latest research progress in the application of MOFs for precision phototherapy in breast cancer treatment. It emphasizes their role as a direct photosensitizer (PS), photothermal agent (PTA), or multifunctional nanocarrier for PDT, PTT, and synergistic phototherapy (including PDT/PTT, chemo/phototherapy, and immunotherapy/phototherapy). The design strategy and therapeutic effect of MOFs for phototherapy of breast cancer are critically discussed. In addition, the current bottlenecks and future perspectives are outlined to facilitate the clinical translation of MOF-based breast cancer treatment platforms. Full article

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that relies on the activation of photosensitizers (PS) by specific wavelengths of light to generate reactive oxygen species (ROS), resulting in localized cytotoxicity with relative sparing of healthy tissues. Depending on the PS properties, light dose, and intrinsic cellular features, PDT can elicit multiple cell death pathways, including apoptosis, necrosis, and autophagy. Increasing evidence indicates that PDT is also a potent inducer of ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation (LPO), glutathione (GSH) depletion, and inactivation of glutathione peroxidase 4 (GPX4). PDT-derived ROS promote ferroptosis both indirectly by exhausting antioxidant defenses and directly by peroxidizing PUFAs within membrane phospholipids. At the same time, intense oxidative stress generated by PDT can activate adaptive responses such as mitophagy, a selective autophagic process that removes damaged mitochondria to limit ROS production and preserve redox homeostasis. Ferroptosis and mitophagy are therefore tightly interconnected, functioning as opposing yet complementary regulators of cell fate. PDT emerges as a key upstream modulator of the ferroptosis–mitophagy balance, as spatially and temporally confined oxidative stress can shift cellular responses from adaptive mitochondrial quality control to irreversible ferroptotic injury. Despite growing interest in both PDT and ferroptosis, their mechanistic interplay, particularly in relation to mitophagy, remains underexplored. This narrative review provides an integrated overview of current knowledge on how PDT influences ferroptosis and mitophagy, highlighting the molecular mechanisms that connect these pathways and discussing their implications for improving therapeutic efficacy and overcoming resistance. Full article

Photodynamic therapy is a cancer treatment that relies on a photosensitizer (PS) to generate reactive oxygen species upon light activation, thereby destroying cancer cells. The photophysical properties of porphyrins make them effective PSs, while nanoparticles (NPs) enhance their delivery and stability. The bioavailability and targeting efficiency of NPs-PS complexes may be improved through transport via human serum albumin (HSA). This study investigates the HSA binding affinity with 5,10,15,20-(Tetra-4-carboxyphenyl)porphyrin (TCPP) and with TiO₂-TCPP complexes. The interactions were analyzed using UV-Vis absorption, laser-induced fluorescence (LIF), and FTIR spectroscopy. Molecular docking was performed and provided consistent binding constant values for the TCPP–HSA complex with UV-Vis absorption measurements. LIF data revealed a slightly lower affinity when compare free porphyrin with TiO₂-TCPP, possibly due to competitive binding between TiO₂ and HSA. Docking simulations indicated that TCPP favorably interacts with amino acid residues located in subdomains IB and IIIA of HSA, supporting a preferential binding near Sudlow site I. FTIR measurements revealed conformational changes in HSA for both its interactions with TCPP and TiO₂-TCPP, including alterations in α-helical content and reorganization of the hydrogen bonding network within the polypeptide backbone. Full article

The development of efficient and recyclable catalysts is a central pursuit in modern chemistry. Homogeneous catalysts, while effective, often suffer from challenges in separation and recovery, driving the exploration of heterogeneous systems. In this context, this study introduces a novel composite photocatalyst, Ru(bpy)₂(bda)-Ru(bda)(cp)₂@DE (PS/Cat@DE), synthesized by attaching a catalyst (Cat) and a photosensitizer (PS) to diatomaceous earth (DE). The hypothesis that covalently binding the photosensitizer and photocatalyst to the surface of DE could enhance their reactivity and may protect them from degradation was supported by the enhanced photocatalytic performance observed in this study. The composite materials and single components were characterized using UV-Vis and FTIR spectroscopy, as well as SEM, and EDS microscopy. Photocatalytic experiments demonstrated the significantly higher activity of the PS/Cat@DE material compared to equivalent concentrations of the single photosensitizer or photocatalyst components, indicating the crucial role of DE in promoting oxygen evolution. Full article

Background/Objectives: Boron-dipyrromethene (BODIPY) derivatives are a superior class of fluorophores prized for their exceptional photostability and tunable photophysical properties. While ideal for imaging, their translation to photodynamic therapy (PDT) has been hampered by excitation in the visible range, leading to poor tissue penetration. To overcome this, intense research has focused on developing near-infrared (NIR)-absorbing BODIPY photosensitizers (PS). This review aims to systematically summarize the hierarchical design strategies, from molecular engineering to advanced nanoplatform construction, that underpin the recent progress of NIR-BODIPY PS in therapeutic applications. Methods: We conducted a comprehensive literature review using PubMed, Scopus, and Web of Science databases. The search focused on keywords such as “BODIPY”, “aza-BODIPY”, “near-infrared”, “photodynamic therapy”, “photothermal therapy”, “nanocarriers”, “hypoxia”, “immuno-phototherapy”, and “antibacterial.” This review analyzes key studies describing molecular design, chemical modification strategies (e.g., heavy-atom effect, π-extension), nanoplatform formulation, and therapeutic applications in vitro and in vivo. Results: Our analysis reveals a clear progression in design complexity. At the molecular level, we summarize strategies to enhance selectivity, including active targeting, designing “smart” PS responsive to the tumor microenvironment (TME) (e.g., hypoxia or low pH), and precise subcellular localization (e.g., mitochondria, lysosomes). We then detail the core chemical strategies for achieving NIR absorption and high singlet oxygen yield, including π-extension, the internal heavy-atom effect, and heavy-atom-free mechanisms (e.g., dimerization). The main body of the review categorizes the evolution of advanced theranostic nanoplatforms, including targeted systems, stimuli-responsive ‘smart’ systems, photo-immunotherapy (PIT) platforms inducing immunogenic cell death (ICD), hypoxia-overcoming systems, and synergistic chemo-phototherapy carriers. Finally, we highlight emerging applications beyond oncology, focusing on the use of NIR-BODIPY PS for antibacterial therapy and biofilm eradication. Conclusions: NIR-BODIPY photosensitizers are a highly versatile and powerful class of theranostic agents. The field is rapidly moving from simple molecules to sophisticated, multifunctional nanoplatforms designed to overcome key clinical hurdles like hypoxia, poor selectivity, and drug resistance. While challenges in scalability and clinical translation remain, the rational design strategies and expanding applications, including in infectious diseases, confirm that NIR-BODIPY derivatives will be foundational to the next generation of precision photomedicine. Full article