Photodynamic Activity Research Articles

Synthesis of water‐soluble protoporphyrin IX polymers and their photodynamic application

AbstractProtoporphyrin IX (PpIX) is a photosensitizer used in photodynamic therapy, however, its poor aqueous solubility always presents challenges and limits its application. To solve these problems water‐soluble derivatives of PpIX were synthesized by esterification with polyethylene glycol, and polymerization of the PpIX diol with hexamethylene diisocyanate to form a water‐soluble polyurethane. The polyurethane PpIX derivatives were characterized and showed high levels of singlet oxygen generation. The photodynamic antibacterial activity of the PpIX derivatives were explored on Escherichia coli, Staphylococcus aureus and methicillin‐resistant Staphylococcus aureus indicated that 100% antibacterial killing was achieved with a concentration of 40 μM upon 405 nm irradiation for 5 min. The polyurethane showed high biocompatibility in the dark with a variety of cell lines, but when exposed to 405 nm light (for 5 min) cytotoxic singlet oxygen was generated, resulting in cell death. Importantly, this was also possible with 635 nm illumination. In summary this novel protoporphyrin polyurethane overcomes the issues of solubility, and offers enhanced killing (singlet oxygen) generation with the potential to be used in photodynamic therapy for both antibacterial and anticancer treatment.

Wrapping collagen-based nanoparticle with macrophage membrane for treating multidrug-resistant bacterial infection

Nowadays, multidrug-resistant (MDR) bacterial infectious diseases has become a thorny issue in the healthcare field. Owning to its intrinsic merits, photodynamic therapy (PDT) shows tremendous strengths in fighting against MDR bacterial infections. However, most photodynamic nanoplatforms exhibit unsatisfactory targeting efficiency towards bacteria and infection site, which may compromise the bactericidal effect of PDT. Herein, we firstly reported a bacteria-targeted collagen-based nanoparticle, named Ce6/Col/MM, for treating methicillin-resistant Staphylococcus aureus (MRSA)-infected wound. Ce6/Col/MM was fabricated by wrapping chlorin e6 (Ce6)-loaded collagen-based nanoparticles with macrophage membrane (MM), showing excellent photodynamic activity and good biocompatibility. In vitro studies demonstrated that Ce6/Col/MM could target to bacteria and then exhibit prominent antibacterial capacity against planktonic MRSA under light irradiation. Furthermore, the treatment of MRSA-infected wound in mice with Ce6/Col/MM plus light illumination resulted in potent bacterial inactivation and accelerated wound healing, accompanied by favorable histological compatibility. Collectively, Ce6/Col/MM with superior targeting ability towards bacteria, effective photodynamic antibacterial potency and minimal safety concerns, might be a powerful bactericidal nanoagent for treating infections caused by MDR bacteria.Graphical

Comparative Analysis of Tetra(2-naphthyl)tetracyano-porphyrazine and Its Iron Complex as Photosensitizers for Anticancer Photodynamic Therapy.

Photodynamic therapy (PDT) is a rapidly developing modality of primary and adjuvant anticancer treatment. The main trends today are the search for new effective photodynamic agents and the creation of targeted delivery systems with the function of controlling the release of the agent in the tumor. Recently, the new group of cyanoarylporphyrazine dyes was reported, which combine the properties of photosensitizers and sensors of the local microenvironment. Such unique characteristics allow the release of the photosensitizer from the transport carrier to be assessed in real time in vivo. The aim of the present work was to compare the photophysical and photobiological properties of tetra(2-naphthyl)tetracyanoporphyrazine and its newly synthesized Fe(II) complex. We have shown that the chelation of the Fe(II) cation with the porphyrazine macrocycle leads to a decrease in molar extinction and an increase in the quantum yield of fluorescence and photostability. We demonstrate that the iron cation significantly affects the rate of dye accumulation in cells, the dark toxicity and photodynamic activity, and the direction of the changes depends on the particular cell line. However, in all the cases, the photodynamic index of a metal complex was higher than that of a metal-free base. In general, both of the compounds were found to be very promising for PDT, including for the use with transport delivery systems, and can be recommended for further in vivo studies.

ИЗУЧЕНИЕ ЦИТОТОКСИЧЕСКОГО ДЕЙСТВИЯ МОЛЕКУЛЯРНОГО КОНЪЮГАТА НА ОСНОВЕ ХЛОРИНА Е6

Photodynamic therapy is a clinically approved method of cancer treatment that has shown great potential due to its non-invasiveness and selectivity for proliferating cells. However, the potential of this type of therapy has not been fully exploited, partly due to the lack of ideal photosensitizer drugs. One of the possible strategies for the molecular design of new generation drugs is the inclusion of heavy atoms into the structure of such compounds. The photodynamic and photocytotoxic properties of the newly synthesized molecular conjugate based on Chlorin e6 with europium were studied. Optimal irradiation conditions were selected and effective cell death of Ehrlich's ascitic carcinoma under the action of a molecular conjugate upon irradiation with red light at a wavelength of 645 nm for 20 min was shown. At this stage, the PEI/e6/DTPA/FA/Eu molecular conjugate exhibits confirmed photodynamic activity, which indicates the prospect of further research.

Synthesis, Cellular Uptake, and Photodynamic Activity of Oligogalactosyl Zinc(II) Phthalocyanines.

Invited for this month's cover is the group of Prof. Dennis K. P. Ng at The Chinese University of Hong Kong. The cover picture shows the selective internalization of molecules of a di-galactosyl zinc(II) phthalocyanine into a cancer cell. Upon light irradiation, these molecules are excited and interact with the endogenous oxygen to generate highly reactive singlet oxygen, which oxidatively damages the cellular components, leading to cell death eventually. More information can be found in the Research Article by Dennis K. P. Ng, and co-workers.

Photo-Phytotherapeutic Gel Composed of Copaifera reticulata, Chlorophylls, and k-Carrageenan: A New Perspective for Topical Healing.

Chronic wound healing represents an impactful financial burden on healthcare systems. In this context, the use of natural products as an alternative therapy reduces costs and maintains effectiveness. Phytotherapeutic gels applied in photodynamic therapy (PDT) have been developed to act as topical healing medicines and antibiotics. The bioactive system is composed of Spirulina sp. (source of chlorophylls) and Copaifera reticulata oil microdroplets, both incorporated into a polymeric blend constituted by kappa-carrageenan (k-car) and F127 copolymer, constituting a system in which all components are bioactive agents. The flow behavior and viscoelasticity of the formulations were investigated. The photodynamic activity was accessed from studies of the inactivation of Staphylococcus aureus bacteria, the main pathogen of hospital relevance. Furthermore, in vivo studies were conducted using eighteen rabbits with dermatitis (grade III and IV) in both paws. The gels showed significant antibiotic potential in vitro, eliminating up to 100% of S. aureus colonies in the presence or absence of light. The k-car reduced 41% of the viable cells; however, its benefits were enhanced by adding chlorophyll and copaiba oil. The animals treated with the phytotherapeutic medicine showed a reduction in lesion size, with healing and re-epithelialization verified in the histological analyses. The animals submitted to PDT displayed noticeable improvement, indicating this therapy's viability for ulcerative and infected wounds. This behavior was not observed in the iodine control treatment, which worsened the animals' condition. Therefore, gel formulations were a viable alternative for future pharmaceutical applications, aiming at topical healing.

Front Cover: Synthesis, Cellular Uptake, and Photodynamic Activity of Oligogalactosyl Zinc(II) Phthalocyanines (ChemPlusChem 2/2023)

Front Cover: Synthesis, Cellular Uptake, and Photodynamic Activity of Oligogalactosyl Zinc(II) Phthalocyanines (ChemPlusChem 2/2023)

A hypoxia responsive silicon phthalocyanine containing naphthquinone axial ligands for photodynamic therapy activity

A liposome loaded‑silicon (IV) phthalocyanine (SiPc) containing naphthoquinone axial ligands as hypoxia-responsive a prodrug-like moieties (Prodrug-SiPc), is herein reported. With the help of computational methods, this study assessed the photophysical, photochemical and electrochemical redox properties of the Prodrug-SiPc to elucidate the relationship between material structure and properties. The attachment of the axial quinoid moieties endowed the Prodrug-SiPc with Type I/II photochemical and prodrug-like properties. Following liposomal encapsulation, the therapeutic efficacy of Prodrug-SiPc-liposomes was investigated against Michigan Cancer Foundation-7 (MCF-7) and Henrietta Lacks (Hela) cancer cells as in vitro cancer models and revealed that the as-synthesized Prodrug-SiPc-liposomes are potential photodynamic therapy (PDT) drug candidates. The Prodrug-SiPc-liposome takes full advantage of the hypoxic microenvironment of tumors - a side effect PDT - to trigger therapy, resulting in significantly enhanced efficacy compared to typical PDT. This work highlights the importance of multiple characteristics in designing new and effective photosensitizer candidates.

Green synthesis of carbon quantum dots from plant turmeric holds promise as novel photosensitizer for in vitro photodynamic antimicrobial activity

Research has shown that carbon quantum dots (CQDs) are active as novel carbon nanomaterials in photodynamic therapy due to their excellent photophysical properties. However, previously expensive precursors and time-consuming production processes, as well as complex doping/functionalization forms have limited their economic design and use. In this study, we prepared ST-JHCQDs by a simple and green method using natural plant turmeric as the carbon source, and characterized ST-JHCQDs by physical and optical means. In vitro antibacterial results showed that the antibacterial effects of ST-JHCQDs against E. coli and S. aureus under the irradiation of blue light depended on carbonization degrees, concentration and light duration. Biomolecule leakage and confocal laser scanning microscope analysis showed that ST-JHCQDs were effective in producing reactive oxygen species (ROS) under blue light irradiation, which resulted in disturbance of cell membrane integrity and leakage of intracellular macromolecules in both bacteria. Meanwhile, scanning electron microscopy images showed cell membrane wrinkling and fragmentation, which was consistent with ROS damage, demonstrating the effectiveness of ST-JHCQDs as photosensitizers in vitro photodynamic antimicrobial activity. These experiments show that CQDs prepared from turmeric was a new natural photosensitizer material with great antibacterial potential.

Димеризация фталоцианина алюминия в органической и водно-органической средах

Aluminum phthalocyanine chloride (AlClPc) is a photoactive macroheterocyclic compound, which, in its monomeric form, is used as a photosensitizer (PS) in photodynamic therapy and diagnostics. In this paper, its physicochemical properties were studied in organic (N, N-dimethylformamide, DMF) and aqua-organic (DMF-aqua) media. It has been shown that the hydrophobic properties of AlClPc prevent its widespread use in various pharmacological compositions due to its tendency to aggregate in aqueous solutions, which leads to the formation of non-fluorescent aggregates and a decrease in its photodynamic activity. The geometry and electronic structure of AlClPc in the monomeric and dimerized (H- and 
 J-aggregates) states were studied using quantum-chemical calculations with the help of the electron density functional theory (DFT) method. Different types of orientation during the dimerization of AlClPc molecules are presented: “back to back”, “head to head”, “head to back”, as well as mixed-oriented types. It has been proven that both in DMF and DMF-aqua media, the preferred orientation is “back to back”, without sacrificing the monomeric geometry of the constituent molecules in the dimer. It is shown that in an aqueous organic solvent the AlClPc molecule is easily hydrated with the formation of a coordination bond between the Al atom of the AlClPc molecule and the O atom of the aqua molecule. The bond length is 2.23 Å, and the hydration energy is 16.84 kcal/mol. Hydration promotes the formation of dimers, in which two aqua molecules play the role of "bridges" between two AlClPc molecules. In such dimer, each aqua molecule has two bonds: one coordination bond between its O atom and the Al atom of one of the AlClPc molecules and one hydrogen bond between its H atom and the N atom of another AlClPc molecule. Based on the calculated data obtained, the AlClPc dimers in the DMF medium were assigned to H-aggregates, and in the DMF-water medium, to J-aggregates, respectively.

Antitumor activity of photodynamic therapy with tetracationic derivative of synthetic bacteriochlorin in spheroid culture of liver and colon cancer cells

Efficient screening of photosensitizers (PS) as well as studying their photodynamic activity, especially PS excited in the near-infrared region, require informative in vitro models to adequately reflect the architecture, thickness, and intercellular interactions in tumors. In our study, we used spheroids formed from human colon cancer HCT-116 cells and liver cancer Huh7 cells to assess the phototoxicity of a new PS based on tetracationic derivative of synthetic bacteriochlorin (BC4). We optimized conditions for the irradiation regime based on the kinetics of BC4 accumulation in spheroids and kinetics of spheroid growth. Although PS accumulated more efficiently in HCT-116 cells, characterized by more aggressive growth and high proliferative potential, they were less susceptible to the photodynamic therapy (PDT) compared to the slower growing Huh7 cells. We also showed that 3D models of spheroids were less sensitive to BC4 than conventional 2D cultures with relatively identical kinetics of drug accumulation. Our findings suggest that BC4 is a perspective agent for photodynamic therapy against cancer cells.

Photodynamic Lignin Hydrogels: A Versatile Self-Healing Platform for Sustained Release of Photosensitizer Nanoconjugates

A multifunctional hydrogel that combines the properties of pH-responsiveness as well as controlled release holds enormous potential for antimicrobial photodynamic therapy through the development of wound dressings and coatings. Utilization of lignin (a biodegradable and cost-effective biopolymer) could be advantageous as a sustainable alternative over the conventional hydrogels for photodynamic therapy, which is an underexplored area. In this work, the lignin-based hydrogel was developed, which was found to have remarkable self-healing properties. Moreover, the lignin-based photodynamic hydrogels designed via in situ and ex situ methods were found to be transparent enough (through the variation of lignin concentration) to be utilized for photodynamic therapy applications. The in situ method is an example of lignin hydrogel synthesis which is advantageous as it saves multiple reaction steps of nanoparticle synthesis and incorporation into the hydrogel. However, for the demonstration of photodynamic effect, the lignin-based hydrogels were doped with a photosensitizer (Rose Bengal, RB) and also with RB-conjugated lignin-derived silver nanocomplexes (RB@L-AgNCs). The developed lignin-based nanocomposite hydrogels were characterized through various methods including UV–vis spectroscopy, HRTEM, BET, XRD, FESEM, rheology, and FTIR to determine their material properties. Interestingly, the lignin hydrogels were found to possess pH-responsive properties for controlled release of the incorporated nanoagents. Antimicrobial photodynamic therapy studies were performed using lignin-based nanocomposite hydrogels as well as bare lignin hydrogels through utilization of a green laser for a short time (3 min). Mechanistically, it was observed that the nanocomposite-doped hydrogel worked much better as compared to the native lignin hydrogel due to higher reactive oxygen species (ROS) generation. Furthermore, the antimicrobial photodynamic activity of the developed lignin-based nanocomposite hydrogels was validated through fluorescence microscopy studies (live–dead cell imaging). These developed biodegradable lignin-based nanocomposite hydrogels can be efficiently used for the development of wound dressings and nanocoatings over various surfaces for stimuli responsive antimicrobial effect.

Photodynamic Polymers Constituted by Porphyrin Units as Antibacterial Materials

Photodynamic inactivation of microorganisms has emerged as a promising strategy to kill and eradicate pathogens. In this work, two polymers, TCP-P and ZnTCP-P, were synthesized by oxidative polymerization of 5,10,15,20-tetrakis [3-(N-ethylcarbazoyl)]porphyrin and its complex with Zn(II). Solid polymers consist of rods (diameter 100 nm, length ~100–500 nm) that form microporous structures on a surface. UV-visible absorption spectra in solution showed the Soret and Q bands characteristic of the corresponding constitutional porphyrins. In addition, the polymers presented two red emission bands with quantum yields ΦF = 0.11 for TCP-P and ΦF = 0.050 for ZnTCP-P. These compounds sensitized the production of singlet molecular oxygen with quantum yields of ΦΔ~0.3. Thus, the spectroscopic and photodynamic properties of the porphyrin units were maintained in the conjugates. The photodynamic activity induced by both polymers was tested to inactivate S. aureus. In cell suspensions, TCP-P was more effective than ZnTCP-P in killing bacteria. Viable S. aureus cells were not detected using 4 µM TCP-P after 20 min of irradiation. Moreover, both polymers showed a high photocytotoxic activity to eradicate S. aureus cells attached to a surface. The results indicate that these conjugated polymers can act as effective antimicrobial agents to photoinactivate pathogens.

The bromoporphyrins as promising anti-tumor photosensitizers in vitro.

The synthesis of ideal photosensitizers (PSs) is considered to be the most significant bottleneck in photodynamic therapy (PDT). To discover novel PSs with excellent photodynamic anti-tumor activities, a series of novel photosensitizers 5,15-diaryl-10,20-dibromoporphyrins (I1-6) were synthesized by a facile method. Compared with hematoporphyrin monomethyl ether (HMME) as the representative porphyrin-based photosensitizers, it is found that not only the longest absorption wavelength of all compounds was red-shifted to therapeutic window (660nm) of photodynamic therapy, but also the singlet oxygen quantum yields were significantly increased. Furthermore, all compounds exhibited lower dark toxicity (except I2) and stronger phototoxicity (except I4) against Eca-109 tumor cells than HMME. Among them, I3 possessed the highest singlet oxygen quantum yield (ΦΔ = 0.205), the lower dark toxicity and the strongest phototoxicity (IC50 = 3.5μM) in vitro. The findings indicated the compounds I3 had the potential to become anti-tumor agents for PDT.

Synthesis of novel heterogeneous photocatalysts based on Rose Bengal for effective wastewater disinfection and decontamination

Anionic photosensitizers such as rose Bengal (RB) exhibit low efficiency in the photoinactivation of Gram-negative bacteria. Different strategies have been developed to improve their efficiency being the most effective the addition of the photosensitizer to organic cationic materials. In this context, we have designed the synthesis of a novel heterogeneous photocatalyst based on silica in which the oxidizing properties of singlet oxygen photogenerated by RB have been combined with the chemoattraction of the bacteria to the cationic chains and their biocidal action. Thus, RB and cationic chains have been covalently linked to glass wool to obtain a photocatalyst that showed a highly efficient photodynamic activity against the Gram-positive (Enterococcus faecalis) and Gram-negative (Escherichia coli) bacteria. In addition, the new heterogeneous photocatalyst also resulted to be efficient in the decontamination of drugs such as diclofenac under visible light irradiation.

Ti3C2 MXene/gold nanorods-based hybrid nanoparticles with photodynamic antibacterial activities

Ti3C2 MXene/gold nanorods-based hybrid nanoparticles with photodynamic antibacterial activities

ФОТОДИНАМИЧЕСКИ-АКТИВНЫЕ ПРЕПАРАТЫ В ЛЕЧЕНИИ РАЗЛИЧНЫХ ЗАБОЛЕВАНИЙ

A multifactorial effect on damaged tissues of the body in the process of a photosensitive reaction in photodynamic therapy is carried out. It includes the killing of pathologically altered cells with intensive production of reactive oxygen species, the effect on blood vessels and the activation of the body's immune system. The effectiveness of this method depends on the properties of photosensitizing drugs, namely, their selectivity, the ability to photoproduce reactive particles and ability to absorb in the near infrared spectrum. This review discusses three generations of photosensitizers. The first is the photodynamically active compound hematoporphyrin «Photofrin I». Taking into account the shortcomings of the first generation of drugs, such as: the complexity of the chemical composition, moderate photodynamic activity, a high degree of photosensitization of normal skin areas, insufficient selectivity and low optical absorption, second-generation photosensitizers were developed. These include Levulan, Foscan, Talaporfin and others. However, clinical trials of some of them have not been completed due to a number of reasons, to a greater extent, the low effectiveness of drugs or the financial costs of research. The third generation preparations were obtained using the methods of bioconjugation and encapsulation of photosensitizers of previous generations. To date, special attention is paid to the development of new systems for targeted delivery of photosensitizers, such as nanoparticles and monoclonal antibodies, which can significantly reduce the time required for targeted accumulation in tumor tissue.

Synthesis of trans-Substituted Cationic Zinc Porphynates and Study of their Photodynamic Antimicrobial Activity

Synthesis of trans-Substituted Cationic Zinc Porphynates and Study of their Photodynamic Antimicrobial Activity

Uniform π‐Conjugated‐Co‐Oligomer‐Based Nanofibers of Controlled Length with Near‐Infrared Emission, Photodynamic and Photothermal Activities

Abstractπ‐Conjugated‐polymer‐based nanofibers (CPNFs) have attracted considerable interest in the community of nanomedicine owing to their high‐aspect‐ratio architecture and inherent photo‐imaging, photothermal, photodynamic, and photoacoustic properties. However, the preparation of uniform CPNFs of controlled length and composition with near‐infrared emission (NIR), photothermal and photodynamic activity remains in its infancy. A novel block copolymer consisting of a donor‐acceptor‐donor (D‐A‐D) π‐conjugated co‐oligomer with a diketopyrrolopyrrole (DPP) unit as electron‐deficient acceptor flanked by oligo(p‐ phenylene ethynylene) (OPE) as an electron‐rich donor and a poly(2‐vinylpyridine) (P2VP) block (OPE4‐DPP‐OPE4‐b‐P2VP44, the subscripts describe the extra and average number of repeat units for π‐conjugated OPE segment and P2VP block, respectively) is designed and synthesized. By using the self‐seeding approach of living crystallization‐drive self‐assembly (CDSA), uniform CPNFs containing a D‐A‐D OPE4‐DPP‐OPE4 core and a P2VP corona with tunable length from 31 to 611 nm are generated. The resulting CPNFs exhibit NIR emission with a peak at 837 nm. The CPNFs also can serve as a photosensitizer to efficiently produce single oxygen and show a photothermal effect upon 660 nm irradiation. To the author's best knowledge, it is the first report on the generation of uniform CPNFs of controlled length with NIR emission, and photodynamic and photothermal activities by living CDSA.

Synthesis and Characterization of a Polydioxanone-Coated Dipeptide-Functionalized Magnetic γ-Fe2O3 Nanoparticles-Modified PES Membrane and Its Biological Applications

This work is focused on the synthesis of leucyl-glycine-functionalized γ-Fe2O3 magnetic nanoparticles coated by polydioxanone (γ-Fe2O3-CA-Leu-Gly-PDX) as a polyethersulphone (PES) membrane for biotechnological applications. The physicochemical characteristics were investigated by FT-IR, SEM, XRD, a vibrating sample magnetometer (VSM), and ICP-OES. The present investigation also centered on the several biological activities of γ-Fe2O3-CA-Leu-Gly-PDX. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and metal chelating activity was studied for evaluation of its antioxidant activity potential. It exhibited 100% DPPH radical scavenging and 93.33% metal chelating activity. With applicability to antimicrobial photodynamic therapy, DNA cleavage and antimicrobial activity, the cell viability of γ-Fe2O3-CA-Leu-Gly-PDX was investigated in detail. The γ-Fe2O3-CA-Leu-Gly-PDX demonstrated the significant biofilm inhibition activity as being 81.54% and 86.34% for P. aeruginosa and S. aureus, respectively. Moreover, a novel polyethersulphone nanocomposite membrane incorporated with γ-Fe2O3-CA-Leu-Gly-PDX was prepared. The performance of the γ-Fe2O3-CA-Leu-Gly-PDX-blended polyethersulphone (PES) membrane was investigated by measuring the antifouling and E. coli rejection. The nanocomposite membranes demonstrated remarkable antifouling properties in contrast with the pristine PES when BSA (bovine serum albumin) and E. coli were filtrated. A complete rejection was obtained by the composite membrane. After an application of the membrane study, the modified polyethersulphone (PES) membrane blended with γ-Fe2O3-CA-Leu-Gly-PDX removed 100% of the E. coli.