Porphyrin Photosensitizers Research Articles

Photo-Triggered Fluorescence Polyelectrolyte Nanoassemblies: Manipulate and Boost Singlet Oxygen in Photodynamic Therapy.

Photodynamic therapy (PDT) is a clinically approved therapeutic modality that has shown great potential for cancer treatment. However, there exist two major problems hindering PDT applications: the nonspecific phototoxicity requiring patients to stay in dark post-PDT, and the limited photodynamic efficiency. Herein, we report a photo-triggered porphyrin polyelectrolyte nanoassembling (photo-triggered PPN) strategy, in which porphyrin photosensitizer and photoswitchable energy accepter are assembled into polyelectrolyte micelles by a combined force of charge interaction and metal-ligand coordination. The polyelectrolyte-based PPN exhibits good biocompatibility, and bestows a unique "confining isolated" inner microenvironment for fully overcoming the π-π stacking of porphyrins with significant photodynamic efficiency (123-fold enhancement). Due to the high Förster resonance energy transfer (FRET) (91.5%) between porphyrin and photoswitch in closed-form, we could use light as a specific trigger to modulate photoswitch between closed- and open-form, and manipulate the 1O2 generation in three stages: pre-PDT (quenching 1O2 generation), during PDT (activating 1O2 generation), and post-PDT (silencing 1O2 generation). This de novo strategy has for the first time realized remotely manipulating and boosting 1O2 generation in PDT, well resolving the critical and general challenges of limited photodynamic efficiency and side effects from nonspecific phototoxicity.

Supramolecular Porphyrin Photosensitizers Based on Host-Guest Recognition for In Situ Bacteria-Responsive Near-Infrared Photothermal Therapy.

Antibiotic resistance resulting from the overuse of antibiotics sets a high challenge for brutal antimicrobial treatment. Although photothermal therapy (PTT) overcomes the awkward situation of antibiotic resistance, it usually mistakenly kills the beneficial bacteria strains when eliminating pernicious bacteria. Specifically recognizing and damaging the target pathogens is urgently required for PTT-mediated sterilization strategy. Based on the host-guest recognition between cucurbit[10]uril (CB[10]) and porphyrins, two water-soluble supramolecular porphyrins are designed and implement selective bactericidal effect via in situ bacteria-responsive near-infrared (NIR) PTT. With the help of CB[10], the π-π stacking and hydrophobic interactions of porphyrins are efficiently inhibited, thus contributing to a good photostability and a high photothermal conversion efficiency. Attributing to the matching reduction potential between facultative anaerobic Escherichia coli (E. coli) and porphyrins, they are selectively in situ reduced into supramolecular phlorin and supramolecular chlorin by E. coli, successfully achieving a selective sterilization against E. coli. In vivo, the in situ bacteria-responsive NIR PTT systems also promote the quick recovery of E. coli-infected abscesses and trauma on mice without inducing obvious systemic toxicity, providing a new alternative to the current antibiotics and helping relieve the global public health crisis of abusive antibiotics.

Photoexcitation and One-Electron Reduction Processes of a CO2 Photoreduction Dyad Catalyst Having a Zinc(II) Porphyrin Photosensitizer.

We have explored the photophysical properties and one-electron reduction process in the dyad photocatalyst for CO2 photoreduction, ZnP-phen=Re, in which the catalyst of fac-[Re(1,10-phenanthoroline)(CO)3Br] is directly connected with the photosensitizer of zinc(II) porphyrin (ZnP), using time-resolved infrared spectroscopy, transient absorption spectroscopy, and quantum chemical calculations. We revealed the following photophysical properties: (1) the intersystem crossing occurs with a time constant of ∼20 ps, which is much faster than that of a ZnP single unit, and (2) the charge density in the excited singlet and triplet states is mainly localized on ZnP, which means that the excited state is assignable to the π-π* transition in ZnP. The one-electron reduction by 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole occurs via the triplet excited state with the time constant of ∼100 ns and directly from the ground state with the time constant of ∼3 μs. The charge in the one-electron reduction species spans ZnP and the phenanthroline ligand, and the dihedral angle between ZnP and the phenanthroline ligand is rotated by ∼24° with respect to that in the ground state, which presumably offers an advantage for proceeding to the next CO2 reduction process. These insights could guide the new design of dyad photocatalysts with porphyrin photosensitizers.

Ion-Engineered Clay Nanozyme via Tumor Microenvironment Remodeling for Enhanced Tumor Therapy.

Metal ions show tremendous promise for tumor therapy due to their critical roles in many important catalytic circulations and immune processes. However, the valence state variability and systemic side-effects of metal ions cause ineffective ion enrichment in tumor cells, which limit their further application. Here, a Mn3+ ion delivery system (Mn-HNT) is constructed based on halloysite nanotubes (HNT) via an ion-engineered strategy. Due to the stabilizing effect of HNT on Mn3+ ions, Mn-HNT not only maintained the valence state of Mn3+ ions, but also presented strong catalase (CAT)- and glutathione oxidase (GSHOx)-like catalytic activity to catalyze O2 generation and GSH consumption to relieve the inhibition of tumor microenvironment on photodynamic therapy (PDT). After further coordination with the photosensitizer porphyrin (TCPP), obtained TCPP-Mn-HNT not only inherited the catalytic properties of Mn-HNT to produce oxygen and consume GSH, but acted as photosensitizer for ROS accumulation to effectively destroy tumor cells. Moreover, TCPP-Mn-HNT can promote the maturation of dendritic cells (≈2.8 times), and present the tumor antigen triggered by PDT to T cells to strengthen high-efficient tumor therapy. The study provides new opportunities for designing metal ion delivery system with versatile biofunctions and offers a paradigm of synergistic metal-ion-mediated tumor therapy.

A Review on Recent Trends in Photo-Drug Efficiency of Advanced Biomaterials in Photodynamic Therapy of Cancer.

Photodynamic Therapy (PDT) has emerged as a highly efficient and non-invasive cancer treatment, which is crucial considering the significant global mortality rates associated with cancer. The effectiveness of PDT primarily relies on the quality of the photosensitizers employed. When exposed to appropriate light irradiation, these photosensitizers absorb energy and transition to an excited state, eventually transferring energy to nearby molecules and generating Reactive Oxygen Species (ROS), including singlet oxygen [1O2]. The ability to absorb light in visible and nearinfrared wavelengths makes porphyrins and derivatives useful photosensitizers for PDT. Chemically, Porphyrins, composed of tetra-pyrrole structures connected by four methylene groups, represent the typical photosensitizers. The limited water solubility and bio-stability of porphyrin photosensitizers and their non-specific tumor-targeting properties hinder PDT effectiveness and clinical applications. Therefore, a wide range of modification and functionalization techniques have been used to maximize PDT efficiency and develop multidimensional porphyrin-based functional materials. Recent progress in porphyrin-based functional materials has been investigated in this review paper, focusing on two main aspects including the development of porphyrinic amphiphiles that improve water solubility and biocompatibility, and the design of porphyrin-based polymers, including block copolymers with covalent bonds and supramolecular polymers with noncovalent bonds, which provide versatile platforms for PDT applications. The development of porphyrin-based functional materials will allow researchers to significantly expand PDT applications for cancer therapy by opening up new opportunities. With these innovations, porphyrins will overcome their limitations and push PDT to the forefront of cancer treatment options.

Novel Cyanide-Containing Porphyrins: Unleashing In Vitro Photodynamic Therapy Potential

Porphyrins, a class of four-pyrrole nitrogen heterocyclic compounds, have been used in photodynamic cancer therapy. In this study, three distinct pyridine cationic porphyrin photosensitizers were synthesized, each possessing unique side chains containing cyanide groups (H2-P1∼H2-P3). These photosensitizers were prepared using innovative synthetic methods. Subsequently, their theoretical photophysical properties were investigated using density functional theory (DFT). Notably, this research revealed that H2-P2 exhibits the smallest band gap (2.3548 eV) and the lowest energy gap (ΔEST =0.67 eV). Simultaneously, it was confirmed that these three photosensitizers could indeed produce singlet oxygen under illumination using DPBF as a singlet oxygen probe. Additionally, TPP was uesed as a reference to calculate the singlet oxygen yield for all three compounds, with H2-P2 demonstrating the highest yield (ΦΔ = 0.74). The experimental results aligned with the theoretical predictions. The phototoxicity and dark toxicity of the three photosensitizers were further evaluated using the MTT test. Remarkably, H2-P2 exhibited the highest phototoxicity toward HepG2 cancer cells (IC50<9.1 nM), while the lowest dark toxicity toward HUVEC cells (IC50>10 μM). These findings were supported by additional experiments involving cell staining and measurement of reactive oxygen species.

Porphyrin photosensitizer molecules as effective medicine candidates for photodynamic therapy: electronic structure information aided design.

Traditional photosensitizers (PS) in photodynamic therapy (PDT) have restricted tissue penetrability of light and a lack of selectivity for tumor cells, which diminishes the efficiency of PDT. Our aim is to effectively screen porphyrin-based PS medication through computational simulations of large-scale design and screening of PDT candidates via a precise description of the state of the light-stimulated PS molecule. Perylene-diimide (PDI) shows an absorption band in the near-infrared region (NIR) and a great photostability. Meanwhile, the insertion of metal can enhance tumor targeting. Therefore, on the basis of the original porphyrin PS segments, a series of metalloporphyrin combined with PDI and additional allosteric Zn-porphyrin-PDI systems were designed and investigated. Geometrical structures, frontier molecular orbitals, ultraviolet-visible (UV-vis) absorption spectra, adiabatic electron affinities (AEA), especially the triplet excited states and spin-orbit coupling matrix elements (SOCME) of these expanded D-A porphyrin were studied in detail using the density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods. PS candidates, conforming type I or II mechanism for PDT, have been researched carefully by molecular docking which targeted Factor-related apoptosis (Fas)/Fas ligand (Fasl) mediated signaling pathway. It was found that porphyrin-PDI, Fe2-porphyrin-PDI, Zn-porphyrin-PDI, Mg-porphyrin-PDI, Zn-porphyrin combined with PDI through single bond (compound 1), and two acetylenic bonds (compound 2) in this work would be proposed as potential PS candidates for PDT process. This study was expected to provide PS candidates for the development of novel medicines in PDT.

Porphyrin Photosensitizers into Polysaccharide-Based Biopolymer Hydrogels for Topical Photodynamic Therapy: Physicochemical and Pharmacotechnical Assessments.

Photodynamic therapy (PDT) is an emerging treatment modality that utilizes light-sensitive compounds, known as photosensitizers, to produce reactive oxygen species (ROS) that can selectively destroy malignant or diseased tissues upon light activation. This study investigates the incorporation of two porphyrin structures, 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2.) and 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1.), into hydroxypropyl cellulose (HPC) hydrogels for potential use in topical photodynamic therapy (PDT). The structural and compositional properties of the resulting hydrogels were characterized using advanced techniques such as Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), atomic force microscopy (AFM), UV-Visible (UV-Vis) spectroscopy, and fluorescence spectroscopy. FTIR spectra revealed a slight shift of the main characteristic absorption bands corresponding to the porphyrins and their interactions with the HPC matrix, indicating successful incorporation and potential hydrogen bonding. XRD patterns revealed the presence of crystalline domains within the HPC matrix, indicating partial crystallization of the porphyrins dispersed within the amorphous polymer structure. TGA results indicated enhanced thermal stability of the HPC-porphyrin gels compared to 10% HPC gel, with additional weight loss stages corresponding to the thermal degradation of the porphyrins. Rheological analysis showed that the gels exhibited pseudoplastic behavior and thixotropic properties, with minimal impact on the flow properties of HPC by P2.1., but notable changes in viscosity and shear stress with P2.2. incorporation, indicating structural modifications. AFM imaging revealed a homogeneous distribution of porphyrins, and UV-Vis and fluorescence spectroscopy confirmed the retention of their photophysical properties. Pharmacotechnical evaluations showed that the hydrogels possessed suitable mechanical properties, optimal pH, high swelling ratios, and excellent spreadability, making them ideal for topical application. These findings suggest that the porphyrin-incorporated HPC hydrogels have significant potential as effective therapeutic agents for topical applications.

Porphyrin photosensitizers compatible with both aqueous and non-aqueous conditions: Acid dependent spectral, solubility and photocatalytic properties of meso-tetra(pyridyl)porphyrins

The aerobic photooxidation of 1,3-diphenylisobenzofuran (DPBF) as a specific singlet oxygen quencher was studied in the presence of meso-tetra(aryl)porphyrins (aryl = 2-pyridyl, 3-pyridyl and 4-pyridyl) and their diprotonated and hexaprotonated derivatives to investigate the influence of the position of pyridine nitrogen atom, solvent, core protonation (with HCl or dichloroacetic acid) and full protonation of the porphyrins on their photocatalytic activity and photooxidative stability. The pseudo-first order rate constants (kobs) for the oxidation of DPBF with singlet oxygen were determined to compare the relative activity of the photosensitizers. 1,4-benzoquinone as a scavenger of superoxide anion radical provided evidence for the absence of this species in these photocatalytic systems. The singlet oxygen quantum yields (φΔ) of the porphyrin photosensitizers were estimated by determining the initial rate constants for the oxidation of DPBF. H4T(2-Py)P(Cl)2 and H4T(2-Py)P(CHCl2COO)2 were the most efficient photosensitizers of the series of the meso-tetra(2-, 3- or 4-pyridyl)porphyrins and the protonated derivatives.

One-pot synthesis of a porphyrin functionalized metal-organic frameworks as a recyclable visible-light-driven photosensitizer for efficient detoxification of a sulfur mustard simulant in air

Herein, we report a facile one-pot in situ self-assembly approach that enables a porphyrin photosensitizer, [5,10,15,20-tetrakis(4-methoxycarbonylphenyl)porphyrin]-Zn(II) (ZnTPP), to be enshrouded by a zeolitic imidazolate framework-8 (ZIF-8) to afford a novel visible-light-driven heterogeneous photosensitizer, ZnTPP@ZIF-8 composite. The ZnTTP photosensitizer was well dispersed and fully confined within the ZIF-8 crystals and the framework intactness and porosity were well maintained. The as-prepared ZnTPP@ZIF-8 composite integrates the advantages of ZIF-8 MOFs and ZnTTP photosensitizer. It not only can effectively produce both singlet oxygen (1O2) and superoxide ion (∙O2−) under visible light irradiation, but also exhibit high surface area and excellent stability. The structure characterization of ZnTPP@ZIF-8 composite was first carried out, and then this material can be used as a heterogeneous photosensitizer for the rapid and highly selective detoxification of a sulfur mustard simulant (2-chloroethyl ethyl sulfide) into the corresponding much less toxic sulfoxide product with a half-life of only 1.5 min under visible light irradiation at room temperature in air atmosphere. This catalyst can be readily recycled and reused at least six times without obvious loss of catalytic activity. This study will provide us a new strategy for the facile, rapid and environmentally friendly preparation of photosensitizer@MOFs composites and the rapid detoxification of sulfur mustard under ambient conditions in the future.

Decrease of ESKAPE virulence with a cationic heme-mimetic gallium porphyrin photosensitizer: The Trojan horse strategy that could help address antimicrobial resistance

IntroductionEmerging antibiotic resistance among bacterial pathogens has forced an urgent need for alternative non-antibiotic strategies development that could combat drug resistant-associated infections. Suppression of virulence of ESKAPE pathogens' by targeting multiple virulence traits provides a promising approach. ObjectivesHere we propose an iron-blocking antibacterial therapy based on a cationic heme-mimetic gallium porphyrin (GaCHP), which antibacterial efficacy could be further enhanced by photodynamic inactivation. MethodsWe used gallium heme mimetic porphyrin (GaCHP) excited with light to significantly reduce microbial viability and suppress both the expression and biological activity of several virulence traits of both Gram-positive and Gram-negative ESKAPE representatives, i.e., S. aureus and P. aeruginosa. Moreover, further improvement of the proposed strategy by combining it with routinely used antimicrobials to resensitize the microbes to antibiotics and provide enhanced bactericidal efficacy was investigated. ResultsThe proposed strategy led to substantial inactivation of critical priority pathogens and has been evidenced to suppress the expression and biological activity of multiple virulence factors in S. aureus and P. aeruginosa. Finally, the combination of GaCHP phototreatment and antibiotics resulted in promising strategy to overcome antibiotic resistance of the studied microbes and to enhance disinfection of drug resistant pathogens. ConclusionLastly, considering high safety aspects of the proposed treatment toward host cells, i.e., lack of mutagenicity, no dark toxicity and mild phototoxicity, we describe an efficient alternative that simultaneously suppresses the functionality of multiple virulence factors in ESKAPE pathogens.

Fluorescence lifetime imaging and phasor analysis of intracellular porphyrinic photosensitizers applied with different polymeric formulations

The fluorescence lifetime of a porphyrinic photosensitizer (PS) is an important parameter to assess the aggregation state of the PS even in complex biological environments. Aggregation-induced quenching of the PS can significantly reduce the yield of singlet oxygen generation and thus its efficiency as a medical drug in photodynamic therapy (PDT) of diseased tissues. Hydrophobicity and the tendency to form aggregates pose challenges on the development of efficient PSs and often require carrier systems. A systematic study was performed to probe the impact of PS structure and encapsulation into polymeric carriers on the fluorescence lifetime in solution and in the intracellular environment. Five different porphyrinic PSs including chlorin e6 (Ce6) derivatives and tetrakis(m-hydroxyphenyl)-porphyrin and -chlorin were studied in free form and combined with polyvinylpyrrolidone (PVP) or micelles composed of triblock-copolymers or Cremophor. Following incubation of HeLa cells with these systems, fluorescence lifetime imaging combined with phasor analysis and image segmentation was applied to study the lifetime distribution in the intracellular surrounding. The data suggest that for free PSs, the structure-dependent cell uptake pathways determine their state and emission lifetimes. PS localization in the plasma membrane yielded mostly monomers with long fluorescence lifetimes whereas the endocytic pathway with subsequent lysosomal deposition adds a short-lived component for hydrophilic anionic PSs. Prolonged incubation times led to increasing contributions from short-lived components that derive from aggregates mainly localized in the cytoplasm. Encapsulation of PSs into polymeric carriers led to monomerization and mostly fluorescence emission decays with long fluorescence lifetimes in solution. However, the efficiency depended on the binding strength that was most pronounced for PVP. In the cellular environment, PVP was able to maintain monomeric long-lived species over prolonged incubation times. This was most pronounced for Ce6 derivatives with a logP value around 4.5. Micellar encapsulation led to faster release of the PSs resulting in multiple components with long and short fluorescence lifetimes. The hydrophilic hardly aggregating PS exhibited a mostly stable invariant lifetime distribution over time with both carriers. The presented data are expected to contribute to optimized PDT treatment protocols and improved PS-carrier design for preventing intracellular fluorescence quenching. In conclusion, amphiphilic and concurrent hydrophobic PSs with high membrane affinity as well as strong binding to the carrier have best prospects to maintain their photophysical properties in vivo and serve thus as efficient photodynamic diagnosis and PDT drugs.

Effect of diphenylalanine on the functional activity of porphyrin and non-porphyrin photosensitizers solubilized by Pluronic F127

The effect of the diphenylalanine (Phe-Phe) amino acid on the rate of tryptophan photooxidation catalyzed by photosensitizers (PS) of different natures: dimegin (DMG), fluorinated tetraphenylporphyrin (FTPP), photoditazine (PD) and methylene blue (MB) was studied. It was shown that in the presence of Phe-Phe, the effective constant of photooxidation of the substrate catalyzed by DMG, PD and MB in the aqueous phase decreases. However, the introduction of the amphiphilic polymer Pluronic F127 into the systems allows not only to restore, but also to increase the activity of the PS in the processes of photosensitized oxidation. In particular, the activity of dimegin solubilized by Pluronic F127 in the presence of Phe-Phe is higher than the activity of both pure porphyrin and solubilized DMG. In addition, the activity of the hydrophobic FTPP solubilized by Pluronic also increases. At the same time, a study of the luminescence of singlet oxygen generated by solubilized FTPP in the absence and presence of Phe-Phe revealed that the dipeptide does not influence the processes of 1О2 generation. It was suggested that micellar catalysis influences the activity of solubilized PS in the presence of a biologically active dipeptide.

Activity-Based Nitric Oxide-Responsive Porphyrin for Site-Selective and Nascent Cancer Ablation.

Nitric oxide (NO) generated within the tumor microenvironment is an established driver of cancer progression and metastasis. Recent efforts have focused on leveraging this feature to target cancer through the development of diagnostic imaging agents and activatable chemotherapeutics. In this context, porphyrins represent an extraordinarily promising class of molecules, owing to their demonstrated use within both modalities. However, the remodeling of a standard porphyrin to afford a responsive chemical that can distinguish elevated NO from physiological levels has remained a significant research challenge. In this study, we employed a photoinduced electron transfer strategy to develop a panel of NO-activatable porphyrin photosensitizers (NOxPorfins) augmented with real-time fluorescence monitoring capabilities. The lead compound, NOxPorfin-1, features an o-phenylenediamine trigger that can effectively capture NO (via N2O3) to yield a triazole product that exhibits a 7.5-fold enhancement and a 70-fold turn-on response in the singlet oxygen quantum yield and fluorescence signal, respectively. Beyond demonstrating excellent in vitro responsiveness and selectivity toward NO, we showcase the potent photodynamic therapy (PDT) effect of NOxPorfin-1 in murine breast cancer and human non-small cellular lung cancer cells. Further, to highlight the in vivo efficacy, two key studies were executed. First, we utilized NOxPorfin-1 to ablate murine breast tumors in a site-selective manner without causing substantial collateral damage to healthy tissue. Second, we established a nascent human lung cancer model to demonstrate the unprecedented ability of NOxPorfin-1 to halt tumor growth and progression completely. The results of the latter study have tremendous implications for applying PDT to target metastatic lesions.

Microemulsion-Assisted Self-Assembly of Indium Porphyrin Photosensitizers with Enhanced Photodynamic Therapy.

Designing and constructing supramolecular photosensitizer nanosystems with highly efficient photodynamic therapy (PDT) is vital in the nanomedical field. Despite recent advances in forming well-defined superstructures, the relationship between molecular arrangement in nanostructures and photodynamic properties has rarely been involved, which is crucial for developing stable photosensitizers for highly efficient PDT. In this work, through a microemulsion-assisted self-assembly approach, indium porphyrin (InTPP) was used to fabricate a series of morphology-controlled self-assemblies, including nanorods, nanospheres, nanoplates, and nanoparticles. They possessed structure-dependent 1O2 generation efficiency. Compared with the other three nanostructures, InTPP nanorods featuring strong π-π stacking, J-aggregation, and high crystallinity proved to be much more efficient at singlet oxygen (1O2) production. Also, theoretical modeling and photophysical experiments verified that the intermolecular π-π stacking in the nanorods could cause a decreased singlet-triplet energy gap (ΔEST) compared with the monomer. This played a key role in enhancing intersystem crossing and facilitating 1O2 generation. Both in vitro and in vivo experiments demonstrated that the InTPP nanorods could trigger cell apoptosis and tumor ablation upon laser irradiation (635 nm, 0.1 W/cm2) and exhibited negligible dark toxicity and high phototoxicity. Thus, the supramolecular self-assembly strategy provides an avenue for designing high-performance photosensitizer nanosystems for photodynamic therapy and beyond.

Porphyrin Derivative with Binary Properties of Photodynamic Therapy and Water-Dependent Reversible Photoacidity Therapy for Treating Hypoxic Tumor.

Porphyrin photosensitizers are the classic drugs in clinical photodynamic therapy (PDT), but the hypoxia of tumor environment and the rapid oxygen consumption of PDT severely weaken their therapeutic effect. A recently reported water-dependent reversible photoacidity therapy (W-RPAT) is O2-independence, providing a solution for the treatment of hypoxic tumors. In this work, TPP-O-PEG5, a porphyrin derivative with binary properties of PDT and W-RPAT, is designed and synthesized for the first time. The nanoparticles (NPs) of TPP-O-PEG5 encapsulated with DSPE-mPEG2000, an amphiphilic polymer approved by Food and Drug Administration, can simultaneously produce reactive oxygen species and H+ under irradiation of a 660nm laser, and revert the H+ back under darkness, presenting strong phototoxicity to multiple tumor cell lines with no obvious difference between the IC50 values tested under normoxic (≈20% O2) and hypoxic (<0.5% O2) conditions. Excitingly, in vivo experiments show that the therapeutic effect of TPP-O-PEG5 NPs on large hypoxic tumors is better than that of NPe6, a clinical porphin PDT drug. This work provides a novel strategy for porphyrin photosensitizers to break through the limitation of hypoxic environment, and significantly improve the phototherapeutic effect on hypoxic tumors.

Synthesis of asymmetric cationic zinc porphyrin photosensitizer containing thiophene group for photodynamic therapy in vitro and theoretical calculation of DFT

Porphyrins, as photosensitizers for photodynamic therapy, is used to treat various cancers. In this study, three different side-chain variants of thiophene-zinc porphyrins were synthesized (Zn-P1, Zn-P2, and Zn-P3). Among the synthesized compounds, Zn-P1 exhibited the highest activity and demonstrated superior singlet oxygen generation capability according to both density functional theory calculations and singlet oxygen generation experiments. Our cytotoxicity assays revealed that Zn-P1 exhibited remarkable phototoxicity along with a pronounced selectivity for HepG2 cells. This selectivity was confirmed by cell staining experiments, which showed obvious apoptotic processes. Further insight into this anticancer mechanism was provided by cell reactive oxygen species experiments, which explained the induction of cancer cell apoptosis. Light-activated production of reactive oxygen species by photosensitizers initiates the apoptotic cascade in cancer cells. This study highlights the utility of cationic porphyrin photosensitizer complexes in photodynamic therapy and provides new insights for the development of innovative photosensitizers in cancer treatment.

Novel porphyrin derivative containing cations as new photodynamic antimicrobial agent with high efficiency.

Bacterial infections from chronic wounds affect about 175 million people each year and are a significant clinical problem. Through the integration of photodynamic therapy (PDT) and chemotherapy, a new photosensitizer consisting of ammonium salt N,N-bis-(2-hydroxyethyl)-N-(6-(4-(10,15,20-trimesitylporphyrin-5-yl) phenoxy) hexane)-N-methanaminium bromide, TMP(+) was successfully synthesized with a total reaction yield of 10%. The novel photosensitizer consists of two parts, a porphyrin photosensitizer part and a quaternary ammonium salt part, to achieve the synergistic effect of photodynamic and chemical antibacterial activity. With the increase of TMP(+) concentration, the diameter of the PCT fiber membranes (POL/COL/TMP(+); POL, polycaprolactone; COL, collagen) gradually increased, which was caused by the charge of the quaternary ammonium salt. At the same time, the antibacterial properties were gradually improved. We finally selected the PCT 0.5% group for the antibacterial experiment, with excellent performance in fiber uniformity, hydrophobicity and biosafety. The antibacterial experiment showed that the modified porphyrin TMP(+) had a better antibacterial effect than others. In vivo chronic wound healing experiments proved that the antibacterial and anti-inflammatory effect of the PCTL group was the best, further confirmed by H&E histological analysis, immunofluorescence and immunohistochemistry mechanism experiments. This research lays the foundation for the manufacture of novel molecules that combine chemical and photodynamic strategies.

Tracking photoinduced charge separation in a perfluorinated Zn-tetraphenylporphyrin sensitizer

A zinc porphyrin photosensitizer (ZnF20) is investigated for photoinduced charge separation with different electron donors. Probes of optical light absorption and resonance Raman scattering are used to track the evolution of transient species.

Synthesis of three cisplatin-conjugated asymmetric porphyrin photosensitizers for photodynamic therapy.

Photodynamic therapy provides a promising solution for treating various cancer types. In this study, three distinct asymmetric porphyrin-cisplatin complex photosensitizers (ZnPt-P1, ZnPt-P2, and ZnPt-P3) were synthesized, each having unique side chains. Through a set of experiments involving singlet oxygen detection and density functional theory, ZnPt-P1 was demonstrated to have excellent efficacy, exceeding that of ZnPt-P2 and ZnPt-P3. Notably, ZnPt-1 showed significant phototoxicity while maintaining low dark toxicity when tested on HepG2 cells. Additionally, further examination revealed that ZnPt-P1 had the capability to generate reactive oxygen species within cancer cells when exposed to light irradiation. Taken together, these results highlight the potential of ZnPt-P1 as a photosensitizer for use in photodynamic therapy. This study contributes to enhancing cancer treatment methodologies and provides insights for the future development of innovative drugs for photosensitization.