Search Results (35)

Background: Interleukin-15 (IL-15) stimulates the proliferation of natural killer cells or T cells, which, in combination with photodynamic therapy (PDT), has emerged as an effective strategy for cancer photoimmunotherapy. Instead of direct cytokine receptor activation, IL-15 necessitates first binding to the IL-15 receptor α chain subunit (IL-15Rα), followed by trans-presentation to the IL-15 receptor β/γ chain subunit on the effector cells for pharmacologic activation. Therefore, the delivery of IL-15 remains a major challenge owing to its short half-life, its lack of targeting activity, and the limited availability of IL-15Rα. Methods: A co-hitchhiking delivery approach using recombinant IL-15 (rIL-15) and a photosensitizer, pheophorbide A (PhA), is developed for enhanced combinatorial cancer immunotherapy with PDT. A recombinant IL-15Rα-sushi-Fc fusion protein (rILR-Fc) is designed to load rIL-15 through the IL-15Rα sushi domain, which mimics its trans-presentation. Moreover, the Fc moiety of rILR-Fc can load PhA based on its high binding affinity. Results: Through self-assembly, rILR-Fc/PhA/rIL-15 nanoparticles (NPs) are formulated to co-hitchhike PhA and rIL-15, which improves the tumor accumulation of PhA and rIL-15 through receptor-mediated transcytosis. Moreover, the nanoparticles prolong the blood half-life of rIL-15 but do not alter the elimination rate of PhA from the blood. The rILR-Fc/PhA/rIL-15 NPs effectively elicit potent systemic antitumor immunity and long-lasting immune memory against tumor rechallenge in model mice bearing orthotopic colon tumors. Conclusions: The enhanced antitumor therapeutic effect demonstrates that the co-hitchhiking delivery strategy, optimizing the pharmacokinetics of both the photosensitizer and IL-15, provides a promising strategy for combinatorial photodynamic and IL-15 immunotherapy. Full article

Cytochromes P450 are a superfamily of heme-containing monooxygenases involved in a variety of oxidative metabolic reactions, primarily catalyzing the insertion of an oxygen atom into a C-H bond. CYP102 represents the first example of a bacterial P450 that can be classified as a type II (eukaryotic-like) P450 and functions as a catalytically self-sufficient enzyme. These unique features have made CYP102 an attractive system for studying P450 structure and function. However, an overall picture of the specific amino acid residues that are crucial to the functioning of CYP102 and the effect of mutations on the P450 structure and catalysis is yet to be reported. Such an approach will aid protein engineering approaches used to improve this enzyme. To address this research knowledge gap, we have investigated 105 CYP102 crystal structures in this study. We demonstrate that the CYP102 active site is highly dynamic and flexible. Amino acid residues that play critical roles in substrate binding, orientation, and anchoring were identified. Mutational studies highlighted the roles of amino acids and provided possible bioengineering improvement strategies for CYP102. Decoy molecules are a promising agent for deceiving CYP102 and permitting non-native substrates into the active site. Ru(II)-diimine photosensitizers and zinc/cobalt (III) sepulchrate (Co(III)Sep) could be used as alternative electron sources. The present study serves as a reference for understanding the structure–functional analysis of CYP102 family members precisely and of P450 enzymes in general. Significantly, this work contributes to the effort to develop an improved CYP102 enzyme, thereby advancing the field of P450 research and potentially leading to new industrial applications. Full article

Photodynamic therapy (PDT) involves the use of photosensitizers (PSs) that, upon activation by specific wavelengths of light, generate reactive oxygen species (ROS), including singlet oxygen (¹O₂) and hydroxyl radicals (·OH), within the targeted tissue, typically tumor cells. The generated ROS induces cellular damage, disrupts cellular processes, and ultimately leads to apoptosis or necrosis of the tumor cells. However, the clinical application of PDT is significantly hindered by the limited tissue penetration ability of light. To address this limitation, laser-free self-luminescent photosensitive systems have emerged as potential solutions for achieving deep-tissue PDT and imaging. This review provides a comprehensive analysis of various laser-independent photosensitive systems, with a particular emphasis on those based on resonance energy transfer (RET), chemically induced electron exchange luminescence (CIEEL), and Cherenkov radiation energy transfer (CRET). The aim is to offer a theoretical framework for the development of novel photodynamic systems and to reassess the application potential of certain previously overlooked photosensitizers (PSs). Full article

Photodynamic therapy (PDT) involves the topical application of a photosensitizer and its activation by visible light, leading to the generation of protoporphyrin IX (PpIX) and reactive oxygen species. Daylight photodynamic therapy (dPDT), a variant utilizing natural sunlight as the energy source, enhances procedural flexibility by eliminating the need for specialized equipment. dPDT has been effectively used in dermatology to treat various cutaneous disorders, including neoplastic and infectious diseases. Traditionally, skin preparation and photosensitizer application are performed by trained practitioners, limiting the accessibility of dPDT for broader populations. However, recent studies suggest that these preparatory steps can be managed by patients or caregivers, enabling fully self-applied, home-based dPDT protocols. This review systematically examines the current evidence on self-applied dPDT (SA-dPDT), emphasizing molecular mechanisms and its efficacy in managing premalignant and other cutaneous conditions. Full article

The combination of photodynamic therapy (PDT) and pneumatotherapy is emerging as one of the most effective strategies for increasing cancer treatment efficacy while minimizing side effects. Photodynamic forces affect nitric oxide (NO) levels as activated photosensitizers produce NO, and NO levels in the tumor and microenvironment directly impact tumor cell responsiveness to PDT. In this paper, 3-benzenesulfonyl-4-(1-hydroxy ether)-1,2,5-oxadiazole-2-oxide NO donor–silicon phthalocyanine coupling (SiPc–NO) was designed and prepared into self-assembled nanoparticles (SiPc–NO@NPs) by precipitation method. By further introducing arginyl-glycyl-aspartic acid (RGD) on the surface of nanoparticles, NO-photosensitizer delivery systems (SiPc–NO@RGD NPs) with photo-responsive and tumor-targeting properties were finally prepared and preliminarily evaluated in terms of their formulation properties, NO release, and photosensitizing effects. Furthermore, high reactive oxygen species (ROS) generation efficiency and high PDT efficiency in two breast cancer cell lines (human MCF-7 and mouse 4T1) under irradiation were also demonstrated. The novel SiPc–NO@RGD NPs show great potential for application in NO delivery and two-photon bioimaging-guided photodynamic tumor therapy. Full article

Photoactive artificial nanocatalysts that mimic natural photoenergy systems can yield clean and renewable energy. However, their poor photoabsorption capability and disfavored photogenic electron–hole recombination hinder their production. Herein, we designed two nanocatalysts with various microstructures by combining the tailored self-assembly of the meso-tetra(p-hydroxyphenyl) porphine photosensitizer with the growth of titanium dioxide (TiO₂). The porphyrin photoabsorption antenna efficiently extended the absorption range of TiO₂ in the visible region, while anatase TiO₂ promoted the efficient electron–hole separation of porphyrin. The photo-induced electrons were transferred to the surface of the Pt co-catalyst for the generation of hydrogen via water splitting, and the hole was utilized for the decomposition of methyl orange dye. The hybrid structure showed greatly increased photocatalytic performance compared to the core@shell structure due to massive active sites and increased photo-generated electron output. This controlled assembly regulation provides a new approach for the fabrication of advanced, structure-dependent photocatalysts. Full article

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. Full article

The integration of two-dimensional Ti₃C₂T_x nanosheets and other materials offers broader application options in the antibacterial field. Ti₃C₂T_x-based composites demonstrate synergistic physical, chemical, and photodynamic antibacterial activity. In this review, we aim to explore the potential of Ti₃C₂T_x-based composites in the fabrication of an antibiotic-free antibacterial agent with a focus on their systematic classification, manufacturing technology, and application potential. We investigate various components of Ti₃C₂T_x-based composites, such as metals, metal oxides, metal sulfides, organic frameworks, photosensitizers, etc. We also summarize the fabrication techniques used for preparing Ti₃C₂T_x-based composites, including solution mixing, chemical synthesis, layer-by-layer self-assembly, electrostatic assembly, and three-dimensional (3D) printing. The most recent developments in antibacterial application are also thoroughly discussed, with special attention to the medical, water treatment, food preservation, flexible textile, and industrial sectors. Ultimately, the future directions and opportunities are delineated, underscoring the focus of further research, such as elucidating microscopic mechanisms, achieving a balance between biocompatibility and antibacterial efficiency, and investigating effective, eco-friendly synthesis techniques combined with intelligent technology. A survey of the literature provides a comprehensive overview of the state-of-the-art developments in Ti₃C₂T_x-based composites and their potential applications in various fields. This comprehensive review covers the variety, preparation methods, and applications of Ti₃C₂T_x-based composites, drawing upon a total of 171 English-language references. Notably, 155 of these references are from the past five years, indicating significant recent progress and interest in this research area. Full article

Bacillus subtilis ferredoxin:NADP⁺ oxidoreductase (BsFNR) is a thioredoxin reductase-type FNR whose redox properties and reactivity with nonphysiological electron acceptors have been scarcely characterized. On the basis of redox reactions with 3-acetylpyridine adenine dinucleotide phosphate, the two-electron reduction midpoint potential of the flavin adenine dinucleotide (FAD) cofactor was estimated to be −0.240 V. Photoreduction using 5-deazaflavin mononucleotide (5-deazaFMN) as a photosensitizer revealed that the difference in the redox potentials between the first and second single-electron transfer steps was 0.024 V. We examined the mechanisms of the reduction of several different groups of non-physiological electron acceptors catalyzed by BsFNR. The reactivity of quinones and aromatic N-oxides toward BsFNR increased when increasing their single-electron reduction midpoint redox potentials. The reactivity of nitroaromatic compounds was lower due to their lower electron self-exchange rate, but it exhibited the same trend. A mixed single- and two-electron reduction reaction was characteristic of quinones, whereas reactions involving nitroaromatics proceeded exclusively via the one-electron reduction reaction. The oxidation of FADH^• to FAD is the rate-limiting step during the oxidation of fully reduced FAD. The calculated electron transfer distances in the reaction with nitroaromatics were close to those of other FNRs including the plant-type enzymes, thus demonstrating their similar active site accessibility to low-molecular-weight oxidants despite the fundamental differences in their structures. Full article

Photodynamic therapy (PDT) has become an important therapeutic strategy because it is highly controllable, effective, and does not cause drug resistance. Moreover, precise delivery of photosensitizers to tumor lesions can greatly reduce the amount of drug administered and optimize therapeutic outcomes. As alternatives to protein antibodies, peptides have been applied as useful targeting ligands for targeted biomedical imaging, drug delivery and PDT. In addition, other functionalities of peptides such as stimuli responsiveness, self-assembly, and therapeutic activity can be integrated with photosensitizers to yield versatile peptide-based nanosystems for PDT. In this article, we start with a brief introduction to PDT and peptide-based nanosystems, followed by more detailed descriptions about the structure, property, and architecture of peptides as background information. Finally, the most recent advances in peptide-based nanosystems for PDT are emphasized and summarized according to the functionalities of peptide in the system to reveal the design and development principle in different therapeutic circumstances. We hope this review could provide useful insights and valuable reference for the development of peptide-based nanosystems for PDT. Full article

In order to select for further development novel photosensitizers for photodynamic therapy in cutaneous disorders, three unsymmetrical porphyrins, namely 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2), 5-(2-hydroxy-5-methoxyphenyl)-10,15,20-tris-(4-carboxymethylphenyl) porphyrin (P3.2), and 5-(2,4-dihydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P4.2), along with their fully symmetrical counterparts 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5,10,15,20-tetrakis-(4-carboxymethylphenyl) porphyrin (P3.1) were comparatively evaluated. The absorption and fluorescence properties, as well as atomic force microscopy measurements were performed to evaluate the photophysical characteristics as well as morphological and textural properties of the mentioned porphyrins. The cellular uptake of compounds and the effect of photodynamic therapy on the viability, proliferation, and necrosis of human HaCaT keratinocytes, human Hs27 skin fibroblasts, human skin SCL II squamous cell carcinoma, and B16F10 melanoma cells were assessed in vitro, in correlation with the structural and photophysical properties of the investigated porphyrins, and with the predictions regarding diffusion through cell membranes and ADMET properties. All samples were found to be isotropic and self-similar, with slightly different degrees of aggregability, had a relatively low predicted toxicity (class V), and a predicted long half-life after systemic administration. The in vitro study performed on non-malignant and malignant skin-relevant cells highlighted that the asymmetric P2.2 porphyrin qualified among the five investigated porphyrins to be a promising photosensitizer candidate for PDT in skin disorders. P2.2 was shown to accumulate well within cells, and induced by PDT a massive decrease in the number of metabolically active skin cells, partly due to cell death by necrosis. P2.2 had in this respect a better behavior than the symmetric P.2.1 compound and the related asymmetric compound P4.2. The strong action of P2.2-mediated PDT on normal skin cells might be an important drawback for further development of this compound. Meanwhile, the P3.1 and P3.2 compounds were not able to accumulate well in skin cells, and did not elicit significant PDT in vitro. Taken together, our experiments suggest that P2.2 can be a promising candidate for the development of novel photosensitizers for PDT in skin disorders. Full article

Commonly used peroxydisulfate (PS) or peroxymonosulfate (PMS) activation methods have been limited in their practical application due to certain drawbacks, such as high cost, high energy consumption and secondary pollution. In this study, a catalyst-free alizarin green (AG) self-activating PMS catalytic system was constructed based on photosensitization properties of dye, which ultimately achieved efficient degradation of the dye activator, also the target pollutant. Here, 52.5% of the 100 mL mixture of 10 mg/L AG decomposed within 60 min with 1 mM PMS under visible-light irradiation, thereby showing a strong pH adaptation. Mechanism of AG self-activating PMS was revealed that the photo-excited AG can effectively transfer photo-induced electrons to PMS for its activation, which generates reactive oxidizing species dominated by singlet oxygen (¹O₂), and supplemented by hydroxyl radical (•OH), superoxide radical (O₂^•−) and sulfate radical (SO₄^•−) to realize the efficient self-degradation of the dye pollutants. Moreover, such self-catalytic system operated well under natural sunlight irradiation, indicating the great application potential in the actual wastewater treatment. Herein, photosensitive dye acted as an ideal PMS activator realizing its efficient self-degradation, which provides a novel idea of “using waste to treat waste” for developing wastewater treatment process in a high-efficiency and low-consumption way. Full article

This study investigated the photolysis and TiO₂-assisted photosensitized degradation of oxytetracycline (OTC) under visible light, the active reactive oxygen species (ROS), and the degradation mechanisms in these two reactions. The results show that the deprotonated OTC could be photolyzed more easily under visible light because of the redshift of its absorption spectrum at high pH values. Due to the TiO₂-assisted self-photosensitized degradation of OTC, OTC removal in the visible light/TiO₂ system was more efficient with the addition of TiO₂, as demonstrated when TiO₂ was replaced with insulator SiO₂. The study’s ROS scavenging experiments show that superoxide radical anion (O₂^•−) ROS was most responsible for the self-sensitized degradation of OTC in both reactions. OTC degradation under the visible light/TiO₂ system was enhanced with increasing TiO₂ load, while the elimination of total organic carbon (TOC) was very limited after 5 h of visible light irradiation. Based on the eight identified transformation products found, five potential reaction mechanisms, including hydroxylation, quinonization, decarbonylation, de-methylation, and dehydration, were proposed for the photolytic and TiO₂-assisted photosensitized degradation mechanisms of OTC under visible light. This study indicates that OTC can degrade under visible light with or without a semiconductor when conditions are suitable. Full article

A facile synthesis of catalytically tunable core-shell CdS-Zn_xMn_1-xS-nanoparticles in conjunction with poly(acrylic acid) (PAA) and porphyrin in an aqueous solution is described in the following: The shell composition of the inorganic nanoparticles is varied to tune the optical properties and to optimize the catalytic activity. Further, the tetravalent cationic 5,10,15,20-tetrakis(4-trimethylammoniophenyl) porphyrin (TAPP) fulfills a triple functionality in the catalyst: as a photosensitizer, as an electrostatic linker connecting the nanoparticles and as a probe to investigate the surface composition of the II-VI semiconducting nanoparticles. Different nanoparticles with varying zinc sulfide/manganese sulfide shell ratios are tested with regard to their photocatalytic behavior by crocin bleaching. The results reveal that the shell composition can be a crucial key to optimize the catalytic activity, which can further be important in tuning the reactivity of related systems. Fundamentally, the stepwise multi-component self-assembly in an aqueous solution has been demonstrated to allow the tuning of optic and catalytic properties of core-shell nanoparticles, a general concept that may be widely applicable. Full article