New Type Of Photosensitizer Research Articles

Molecular Engineering to Boost the Photo-Oxidase Activity of Molecular Rotors in Colorimetric Sensing of Temperatures.

Some organic dyes and photosensitizers with strong visible absorption can behave as photo-responsive oxidase mimics. However, the relationship between the photo-oxidase activity and molecular structure remains unclear to date. In this work, a new type of photosensitizer with the characteristics of molecular rotors, namely DPPy, served as the molecular scaffold for further investigation. To adjust the photocatalytic oxidation ability, DAPy and CBPy were designed and synthesized based on the enhancement and diminishment of the intramolecular charge transfer (ICT) process, respectively. Kinetic studies revealed that DAPy and CBPy both exhibited highly efficient photo-activated oxidase-like activity with 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate, which were in good accordance with their molecular engineering to promote either type I or type II reactive oxygen species (ROS) generation. Impressively a colorimetric method based on the visible light induced oxidase-like activity of molecular rotors was developed to determine the environmental temperature for the first time. Both DAPy and CBPy showed distinct sensitivities toward temperature as compared with several molecular rotors based on the typical fluorimetric detection. This work provides a new strategy for the application of molecular rotors to overcome the non-emissive challenge in temperature sensing.

Highly Efficient Wideband Solar Energy Conversion Employing Singlet-Triplet Transitions

Abstract Panchromatic sunlight energy harvesting is one of the key technologies to improve the performance of photovoltaics; however, while the near-infrared (NIR) light energy is easily converted into heat, energy conversion has proven difficult. In this study, we synthesize a new type of photosensitizer that exhibits singlet–triplet transitions (spin inversion transition, S–T transition) in the NIR region. Using these sensitizers, we achieved highly efficient wideband photoenergy conversion, exceeding 1000 nm, with dye-sensitized solar cells. With only one type of small molecule, this was able to capture half of the photons in sunlight and convert them into electrical energy. This account describes the highly efficient panchromatic energy conversion, and solution-processed multijunction cells using perovskite solar cells.

Covalent Triazine Framework as an Efficient Photocatalyst for Regeneration of NAD(P)H and Selective Oxidation of Organic Sulfide.

Covalent triazine frameworks (CTFs), belonging to the super-family of covalent organic frameworks, have attracted significant attention as a new type of photosensitizer due to the superb light-harvesting ability and efficient charge transfer originating from the large surface area. However, the wide optical band gap in CTFs, which is larger than 3.0 eV, hinders the efficient light harvesting in the visible range. To overcome this limitation, we developed the new type CTFs photocatalyst based on the donor-acceptor conjugation scheme by using melamine (M) and 2,6-diaminoanthraquinone (AQ) as monomeric units. The melamine-2,6-diaminoanthraquinone-based covalent triazine frameworks (M-AQ-CTFs) photocatalyst shows the excellent light-harvesting capacity with high molar extinction coefficient, and the suitable optical band gap involving the internal charge transfer character. Combination of M-AQ-CTFs and artificial photosynthetic system including the organometallic rhodium complex, acting as an electron mediator, exhibited the excellent photocatalytic efficiency for the regeneration of the nicotinamide cofactors such as NAD(P)H. In addition, this photocatalyst showed the high photocatalytic efficiency for the metal-free aerobic oxidation of sulfide. This study demonstrates the high potential of CTFs photocatalyst with the donor-acceptor conjugated scheme can be actively used for artificial photosynthesis.

Self-Assembled Platinum Supramolecular Metallacycles Based on a Novel TADF Photosensitizer for Efficient Cancer Photochemotherapy.

Recently, supramolecular coordination complexes (SCCs) based on photosensitizers as bridging ligands have attracted great attention in cancer therapy owing to their synergistic effect between photodynamic therapy (PDT) and chemotherapy. Herein, a highly emissive supramolecular platinum triangle BTZPy-Pt based on a novel type of photosensitizer BTZPy with thermally activated delayed fluorescence (TADF) was fabricated. The BTZPy and BTZPy-Pt exhibited strong luminescence emission in the visible range with high quantum yields (quantum yields (QYs) for BTZPy and BTZPy-Pt were about 78 and 62% in ethanol solutions, respectively). Additionally, BTZPy had been proved to be an excellent photosensitizer with superior 1O2 generation capability (the 1O2 generation quantum yield reached up to ca. 95%) for PDT. By the combination of the excellent phototoxicity of BTZPy and the antitumor activity of the Pt center, the platinum triangle BTZPy-Pt demonstrated a highly efficient anticancer performance toward HeLa cells (IC50: 0.5 μg mL-1). This study not only provides a blueprint to fabricate new types of photosensitizers but also paves a way to design novel SCCs for efficient PDT.

New-generation photosensitizer-anchored gold nanorods for a single near-infrared light-triggered targeted photodynamic–photothermal therapy

Traditional combined photodynamic and photothermal therapy (PDT/PTT) was limited in clinical treatment of cancer due to the exceptionally low drug delivery efficiency to tumor sites and the activation by laser excitation with different wavelengths. We have accidentally discovered that our synthesized chlorin e6-C-15-ethyl ester (HB, a new type of photosensitizer) be activated by a laser with an excitation wavelength of 660 nm. Herein, we utilized Au nanorods (AuNRs) as 660 nm-activated PTT carriers to be successively surface-functionalized with HB and tumor-targeting peptide cyclic RGD (cRGD) to develop HB-AuNRs@cRGD for single NIR laser-induced targeted PDT/PTT. The HB-AuNRs@cRGD could be preferentially accumulated within tumor sites and rapidly internalized by cancer cells. Thereby, the HB-AuNRs@cRGD could exhibit amplified therapeutic effects by producing both significant reactive oxygen species (ROS) and hyperthermia simultaneously under the guidance of fluorescence imaging. The tumor inhibition rate on ECA109 esophageal cancer model was approximately 77.04%, and the negligible systematic toxicity was observed. This study proposed that HB-AuNRs@cRGD might be a promising strategy for single NIR laser-induced and imaging-guided targeted bimodal phototherapy.

Photodynamic-active smart biocompatible material for an antibacterial surface coating

Here we present a new effective antibacterial material suitable for a coating, e.g., surface treatment of textiles, which is also time and financially undemanding. The most important role is played by hydrophobic carbon quantum dots, as a new type of photosensitizer, produced by carbonization of different carbon precursors, which are incorporated by swelling from solution into various polymer matrices in the form of thin films, in particular polyurethanes, which are currently commercially used for industrial surface treatment of textiles. The role of hydrophobic carbon quantum dots is to work as photosensitizers upon irradiation and produce reactive oxygen species, namely singlet oxygen, which is already known as the most effective radical for elimination different kinds of bacteria on the surface or in close proximity to such modified material. Therefore, we have mainly studied the effect of hydrophobic carbon quantum dots on Staphylococcus aureus and the cytotoxicity tests, which are essential for the safe handling of such material. Also, the production of singlet oxygen by several methods (electron paramagnetic spectroscopy, time-resolved near-infrared spectroscopy), surface structures (atomic force microscopy and contact angle measurement), and the effect of radiation on polymer matrices were studied. The prepared material is easily modulated by end-user requirements.

Interaction of the Sn(IV)-tetra(4-sulfonatophenyl)porphyrin axial complexes with cetyltrimethylammonium bromide: Aggregation and location in micelles, fluorescence properties and photochemical stability

Processes of anionic Sn(IV)-tetra(4-sulfonatophenyl)porphyrin axial complexes with three different ligands (hydroxyl, methoxidol and tyrosine) inclusion in an oppositely charged surfactant in a phosphate buffer at 25 °C were studied. It was shown how the association and localization of the porphyrins into spherical cetyltrimethylammonium bromide micelles affect the aggregation, micelle formation, fluorescent properties and photochemical stability of the systems formed depending on the nature of the Sn(IV)-porphyrin axial ligands. The results obtained determine conditions for quenching or enhancement the fluorescence of the hydrophilic Sn(IV)-porphyrin complexes while reducing the possibility of their photochemical destruction and can be useful in the design of new types of photosensitizers for PDT.

X-ray induced photodynamic therapy with copper-cysteamine nanoparticles in mice tumors

Photodynamic therapy (PDT), a treatment that uses a photosensitizer, molecular oxygen, and light to kill target cells, is a promising cancer treatment method. However, a limitation of PDT is its dependence on light that is not highly penetrating, precluding the treatment of tumors located deep in the body. Copper-cysteamine nanoparticles are a new type of photosensitizer that can generate cytotoxic singlet oxygen molecules upon activation by X-rays. In this paper, we report on the use of copper-cysteamine nanoparticles, designed to be targeted to tumors, for X-ray-induced PDT. In an in vivo study, results show a statistically significant reduction in tumor size under X-ray activation of pH-low insertion peptide-conjugated, copper-cysteamine nanoparticles in mouse tumors. This work confirms the effectiveness of copper-cysteamine nanoparticles as a photosensitizer when activated by radiation and suggests that these Cu-Cy nanoparticles may be good candidates for PDT in deeply seated tumors when combined with X-rays and conjugated to a tumor-targeting molecule.

A Ru(II) polypyridyl complex bearing aldehyde functions as a versatile synthetic precursor for long-wavelength absorbing photodynamic therapy photosensitizers.

The use of Photodynamic Therapy (PDT) for the treatment of several kinds of cancer as well as bacterial, fungal or viral infections has received increasing attention during the last decade. However, the currently clinically approved photosensitizers (PSs) have several drawbacks, including photobleaching, slow clearance from the organism and poor water solubility. To overcome these shortcomings, many efforts have been made in the development of new types of PSs, such as Ru(II) polypyridyl complexes. Nevertheless, most studied Ru(II) polypyridyl complexes have a low absorbance in the spectral therapeutic window. In this work, we show that, by carefully selecting substituents on the polypyridyl complex, it is possible to prepare a complex absorbing at a much higher wavelength. Specifically, we report on the synthesis as well as in-depth experimental and theoretical characterisation of a Ru(II) polypyridyl complex (complex 3) combining a shift in absorbance towards the spectral therapeutic window with a high 1O2 production. To overcome the absence or poor selectivity of most approved PSs into targeted cells/bacteria, they can be linked to targeting moieties. In this line, compound 3 was designed with reactive aldehyde groups, which can be used as a highly versatile synthetic precursor for further conjugation. As a proof of concept, 3 was reacted with benzylamine and the stability of the resulting conjugate 4 was investigated in DMSO, PBS and cell media. 4 showed an impressive ability to act as a PDT PS with no measurable dark cytotoxicity and photocytotoxicity in the low micromolar range against cancerous HeLa cells from 450 nm up to 540 nm.

Photodynamic Therapy Based on Nanoscale Metal-Organic Frameworks: From Material Design to Cancer Nanotherapeutics.

Photodynamic therapy (PDT) is a highly effective, noninvasive, highly selective method for cancer treatment. Nanoscale metal-organic frameworks (NMOFs) are a type of crystalline hybrid material composed of metal centers and organic linkers. Owing to their adjustable structure, easy modification, permanent pores, and good biocompatibility, NMOFs, as either nanophotosensitizers or photosensitizer nanocarriers, have been used in PDT. In this article, we summarize the recent progress in MOF-based nanomaterials for tumor PDT. The MOF-based nanomaterials might open up new avenues for the fabrication of new types of photosensitizers for PDT.

Antimicrobial properties of a new type of photosensitizer derived from phthalocyanine against planktonic and biofilm forms of Staphylococcus aureus

BackgroundBacterial infection is a common clinical problem. Community-associated Staphylococcus aureus (S. aureus) infections can cause extensive tissue damage and necrosis. Photodynamic antimicrobial chemotherapy (PACT) has recently attracted attention as a feasible bacterial therapy. Octa-cationic zinc phthalocyanines are newly identified photosensitizers derived from phthalocyanines bearing 1, 2-ethanediamine groups and quaternized derivatives with different numbers of positive charges (ZnPcn+, n = 4 or 8). Here we report the antimicrobial effects of ZnPcn+-mediated PACT on planktonic and biofilm cultures of S. aureus. MethodsZnPcn+ uptake was detected by photometry after alkaline lysis. Dark-toxicity and light-mediated antimicrobial effects of the drug was determined by the plate count method. The production of intracellular reactive oxygen species (ROS) was detected by flow cytometry. SYTO 9 and propidium iodide (PI) were used to detect the bacterial cell membrane permeability. DNA damage after ZnPcn+-PACT was analyzed by flow cytometry and PI staining. The destruction of biofilm was evaluated by scanning electron microscope (SEM). ResultsThe study of uptake showed that the relative fluorescence intensity of ZnPcn+ in S. aureus peaked at 15 min. Generation of reactive oxygen species (ROS) by ZnPcn+ was enhanced in PACT treatment groups. SYTO 9 and PI staining indicated that cell membrane was damaged. Flow cytometry and PI staining revealed DNA damage. Biofilms were damaged in PACT treatment groups. ConclusionsOur results suggest that light-activated ZnPcn+ can efficiently inhibit planktonic and biofilm cultures of S. aureus.

Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome.

Photodynamic therapy (PDT) is a promising alternative therapy that could be used as an adjunct to chemotherapy and surgery for cancer, and works by destroying tissue with visible light in the presence of a photosensitizer (PS) and oxygen. The PS should restrict tissue destruction only to the tumor and be activated by light of a specific wavelength; both of these properties are required. Arginine-rich peptides, such as cell-penetrating peptides, have membrane-translocating and nuclear-localizing activities, which have led to their application in various drug delivery modalities. Protamine (Pro) is an arginine-rich peptide with membrane-translocating and nuclear-localizing properties. The reaction of an N-hydroxysuccinimide (NHS) ester of rhodamine (Rho) and clinical Pro was carried out in this study to yield RhoPro, and a demonstration of its phototoxicity, wherein clinical Pro improved the effect of PDT, was performed. The reaction between Pro and the NHS ester of Rho is a solution-phase reaction that results in the complete modification of the Pro peptides, which feature a single reactive amine at the N-terminal proline and a single carboxyl group at the C-terminal arginine. This study aimed to identify a new type of PS for PDT by in vitro and in vivo experiments and to assess the antitumor effects of PDT, using the Pro-conjugated PS, on a cancer cell line. Photodynamic cell death studies showed that the RhoPro produced has more efficient photodynamic activities than Rho alone, causing rapid light-induced cell death. The attachment of clinical Pro to Rho, yielding RhoPro, confers the membrane-internalizing activity of its arginine-rich content on the fluorochrome Rho and can induce rapid photodynamic cell death, presumably owing to light-induced cell membrane rupture. PDT using RhoPro for HT-29 cells was very effective and these findings suggest that RhoPro is a suitable candidate as a PS for solid tumors.

Photodynamic Therapy of Human Hepatoma Using Semiconductor Quantum Dots as Sole Photosensitizer

AbstractCurrently, the studies about photodynamic therapy (PDT) of human cancers have made considerable progress and attracted tremendous attention. The existing photosensitizers used for PDT are mainly organic compounds. In order to enhance their photosensitizing efficacy, some studies reported hybrid photosensitizers consisting of inorganic quantum dots (QDs) and organic photosensitizers. Herein, a new type of photosensitizer consisting of sole semiconductor CdTe QDs with good photosensitizing efficacy, excellent water dispersibility, and stability is reported. The photosensitizer is prepared through a facile one‐step strategy using sodium hyaluronate as a stabilizing and targeting agent. Different from most of the previous reports, the as‐prepared QDs do not show inhibition effects on normal cells in the experimental concentration range, but can also be directly utilized as a photosensitizer to specifically and remarkably inhibit the proliferation of human hepatoma cells. Mechanism studies reveal that the QDs could be specifically internalized by hepatoma cells, considerably induce the generation of intracellular reactive oxidative species under light illumination, and significantly induce the necrosis of hepatoma cells. This work provides an inspiration for the direct application of QDs as a new type of photosensitizer to specifically and significantly treat human hepatoma through PDT.

Rapid killing of bacteria by a new type of photosensitizer.

Photodynamic antimicrobial chemotherapy (PACT) uses non-traditional mechanisms (free radicals) and is a highly advocated method with promise of inactivating drug-resistance bacteria for local infections. However, there is no related drug used in clinical practice yet. Therefore, new photosensitizers for PACT are under active development. Here, we report the synthesis of a series of photosensitizers with variable positive charges (ZnPc(TAP)4n+, n=0, 4, 8, 12) and their inactivation against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The binding kinetics of ZnPc(TAP)4n+ to bacteria were measured by flow cytometer. Reactive oxygen species (ROS) generation mechanism of the photosensitizers was studied. The toxicity of these compounds to human blood cells was also evaluated. These compounds showed negligible toxicity against human erythocytes but potent bactericidal effects. The compound with 8 positive charges, ZnPc(TAP)48+, turned out to have the strongest antibacterial effect among this series of compounds, giving IC50 value of 59nM at a light dosage of 5J/cm2 toward E. coli. For a multi-resistant E. coli strain, ZnPc(TAP)48+ decreased the bacteria load by 1000-fold at a concentration of 1μM. Interestingly, ZnPc(TAP)412+, instead of ZnPc(TAP)48+, exhibited the highest amount of binding to bacteria. Flow cytometry studies showed that all PSs have fast binding onto bacteria, reaching saturated binding within 5min. Mechanistically, ZnPc(TAP)412+ generated ROS primarily via Type I mechanism, while ZnPc(TAP)44+ or ZnPc(TAP)48+ created ROS by both type I and type II mechanisms. ZnPc(TAP)4n+ are highly potent, rapid-acting and non-toxic photosensitizers capable of inactivating bacteria.

A New Modality for Cancer Treatment--Nanoparticle Mediated Microwave Induced Photodynamic Therapy.

Photodynamic therapy (PDT) has attracted ever-growing attention as a promising modality for cancer treatment. However, due to poor tissue penetration by light, photodynamic therapy has rarely been used for deeply situated tumors. This problem can be solved if photosensitizers are activated by microwaves (MW) that are able to penetrate deeply into tissues. Here, for the first time, we report microwave-induced photodynamic therapy and exploit copper cysteamine nanoparticles as a new type of photosensitizer that can be activated by microwaves to produce singlet oxygen for cancer treatment. Both in vitro and in vivo studies on a rat osteosarcoma cell line (UMR 106-01) have shown significant cell destruction using copper cysteamine (Cu-Cy) under microwave activation. The heating effects and the release of copper ions from Cu-Cy upon MW stimulation are the main mechanisms for the generation of reactive oxygen species that are lethal bullets for cancer destruction. The copper cysteamine nanoparticle-based microwave-induced photodynamic therapy opens a new door for treating cancer and other diseases.

A new X-ray activated nanoparticle photosensitizer for cancer treatment.

Photodynamic therapy (PDT) has attracted ever-growing attention as a promising modality in the treatment of cancer. However, due to the poor tissue penetration by light, PDT has rarely been applied for treating deep-seated tumors. This problem can be solved if photosensitizers are activated by X-rays, which are able to penetrate deeply into tissues. Previous attempts using X-rays to activate photosensitizers were not very successful, since the traditional PDT photosensitizers could not efficiently be activated with X-rays. Here we exploit copper-cysteamine complex (Cu-Cy) nanoparticles as a new type of photosensitizer activated by X-ray for cancer treatment. The newly invented Cu-Cy nanoparticles can be activated directly by X-rays to produce singlet oxygen. In vitro and in vivo study on human breast cancer cells (MCF-7) have shown significant cell destruction using Cu-Cy nanoparticles under X-ray activation. The Cu-Cy nanoparticles are a novel and potent X-ray activated photosensitizer which can enable PDT for deep cancer treatment.

Rose Bengal-decorated silica nanoparticles as photosensitizers for inactivation ofgram-positive bacteria

A new type of photosensitizer, made from Rose Bengal (RB)-decorated silica (SiO2–NH2–RB) nanoparticles, was developed to inactivate gram-positive bacteria, includingMethicillin-resistant Staphylococcus aureus (MRSA), with high efficiency throughphotodynamic action. The nanoparticles were characterized microscopically andspectroscopically to confirm their structures. The characterization of singlet oxygengenerated by RB, both free and immobilized on a nanoparticle surface, wasperformed in the presence of anthracene-9,10-dipropionic acid. The capability ofSiO2–NH2–RB nanoparticles to inactivate bacteria was tested in vitro on both gram-positive andgram-negative bacteria. The results showed that RB-decorated silica nanoparticles caninactivate MRSA and Staphylococcus epidermidis (both gram-positive) very effectively (upto eight-orders-of-magnitude reduction). Photosensitizers of such design shouldhave good potential as antibacterial agents through a photodynamic mechanism.

Squaraine Dyes for Photodynamic Therapy: Study of Their Cytotoxicity and Genotoxicity in Bacteria and Mammalian Cells¶‡

Halogenated squaraine dyes are characterized by long wavelength absorption (>600 nm) and high triplet yields and therefore represent new types of photosensitizers that could be useful for photodynamic therapy. We have analyzed the cytotoxicity and genotoxicity of the bromo derivative 1, the iodo derivative 2 and the corresponding nonhalogenated dye 3 in the absence and presence of visible light. At concentrations of 1–2 μM, 1 and 2 reduced the cloning efficiency of AS52 Chinese hamster ovary cells to less than 1% under conditions that were well tolerated in the dark. Similarly, the proliferation of L5178Y mouse lymphoma cells was inhibited by photoexcited 1 and 2 with high selectivity. The squaraine 3 was much less efficient. Both 1 and 2 induced only few mutations in the gpt locus of the AS52 cells in the presence of light and were not mutagenic in the dark. No mutagenicity with and without irradiation was observed in Salmonella typhimurium TA100 and TA2638. However, both 1 and 2 plus light increased the frequency of micronuclei in AS52 cells. The results indicate that halogenated squaraines exhibit photobiological properties in vitro that are favorable for photodynamic therapeutical applications.

Photodynamic laser therapy and diagnostics of tumor localization on the basis of new types of photosensitizers

Characteristics of photophysical and photochemical processes in molecules of new symmetric indotricarbocyanine dyes in solutions and biostructures are studied. Correlations between the efficiency of these processes and the specific features of the dye molecule structure, as well as the influence of the physical and chemical parameters of the medium and exciting radiation on these processes are established.

Supramolecular nanocarriers integrated with dendrimers encapsulating photosensitizers for effective photodynamic therapy and photochemical gene delivery

Recently, biomedical applications of dendrimers, three-dimensional tree-like macromolecules, have received much attention. In this paper, we introduce new biomedical applications of functional dendrimers: dendrimers encapsulating photosensitizers composed of a center dye molecule surrounded by poly(benzyl ether) dendrons with ionic peripheral groups as a new type of photosensitizer (PS) for photodynamic therapy (PDT). Dendrimers encapsulating porphyrin and with ionic peripheral groups (DPs) spontaneously formed polyion complex (PIC) micelles through electrostatic interactions with oppositely-charged block copolymers, and showed no self-quenching of the center dye molecule inside the micellar core due to a unique DP structure, leading to remarkable in vitro photocytotoxicity. The DP-incorporated micelles showed successful treatment of choroidal neovascularization (CNV) in rats without any sign of side effects. Thus, the DP-incorporated micelles are expected to be an innovative PS formulation for successful PDT against ophthalmic diseases. In this paper, we also review polymeric micelles incorporating phthalocyanine core dendrimers (DPc) for cancer PDT and novel light-responsive supramolecular gene carriers integrated with DPc for site-directed transfection in vivo.