Potential Application In Photodynamic Therapy Research Articles

Biocompatible Nanocarriers for Enhanced Cancer Photodynamic Therapy Applications.

In recent years, the role of nanotechnology in drug delivery has become increasingly important, and this field of research holds many potential benefits for cancer treatment, particularly, in achieving cancer cell targeting and reducing the side effects of anticancer drugs. Biocompatible and biodegradable properties have been essential for using a novel material as a carrier molecule in drug delivery applications. Biocompatible nanocarriers are easy to synthesize, and their surface chemistry often enables them to load different types of photosensitizers (PS) to use targeted photodynamic therapy (PDT) for cancer treatment. This review article explores recent studies on the use of different biocompatible nanocarriers, their potential applications in PDT, including PS-loaded biocompatible nanocarriers, and the effective targeting therapy of PS-loaded biocompatible nanocarriers in PDT for cancer treatment. Furthermore, the review briefly recaps the global clinical trials of PDT and its applications in cancer treatment.

Lactose-conjugated porphyrin: synthesis and photobiological evaluation as potential agents for photodynamic therapy

Porphyrin-based photosensitizers are conventional photodynamic agents that are used clinically. However, their clinical applications have been overshadowed by poor water solubility. In addition, they have weak tumor selectivity, which may cause undesirable side effects. The preparation of novel porphyrin derivatives has been explored for potential applications in photodynamic therapy (PDT). To achieve this goal, lactose-conjugated porphyrin nanoparticles (Lac-Por NPs) have been synthesized and characterized. PDT with Lac-Por NPs exhibited tumor-specific cytotoxicity in lactose receptor-overexpressing HepG2 cells in vitro and in vivo. In summary, we designed and synthesized lactose conjugate porphyrins with enhanced water solubility and tumor selectivity. This work expands the application range of porphyrin-based photosensitizers for cancer treatment.

Synthesis and Characterization of Polyvinylpyrrolidone-Modified ZnO Quantum Dots and Their In Vitro Photodynamic Tumor Suppressive Action.

Despite the numerous available treatments for cancer, many patients succumb to side effects and reoccurrence. Zinc oxide (ZnO) quantum dots (QDs) are inexpensive inorganic nanomaterials with potential applications in photodynamic therapy. To verify the photoluminescence of ZnO QDs and determine their inhibitory effect on tumors, we synthesized and characterized ZnO QDs modified with polyvinylpyrrolidone. The photoluminescent properties and reactive oxygen species levels of these ZnO/PVP QDs were also measured. Finally, in vitro and in vivo experiments were performed to test their photodynamic therapeutic effects in SW480 cancer cells and female nude mice. Our results indicate that the ZnO QDs had good photoluminescence and exerted an obvious inhibitory effect on SW480 tumor cells. These findings illustrate the potential applications of ZnO QDs in the fields of photoluminescence and photodynamic therapy.

Air-Filled Bubbles Stabilized by Gold Nanoparticle/Photodynamic Dye Hybrid Structures for Theranostics.

Microbubbles have already reached clinical practice as ultrasound contrast agents for angiography. However, modification of the bubbles’ shell is needed to produce probes for ultrasound and multimodal (fluorescence/photoacoustic) imaging methods in combination with theranostics (diagnostics and therapeutics). In the present work, hybrid structures based on microbubbles with an air core and a shell composed of bovine serum albumin, albumin-coated gold nanoparticles, and clinically available photodynamic dyes (zinc phthalocyanine, indocyanine green) were shown to achieve multimodal imaging for potential applications in photodynamic therapy. Microbubbles with an average size of 1.5 ± 0.3 μm and concentration up to 1.2 × 109 microbubbles/mL were obtained and characterized. The introduction of the dye into the system reduced the solution’s surface tension, leading to an increase in the concentration and stability of bubbles. The combination of gold nanoparticles and photodynamic dyes’ influence on the fluorescent signal and probes’ stability is described. The potential use of the obtained probes in biomedical applications was evaluated using fluorescence tomography, raster-scanning optoacoustic microscopy and ultrasound response measurements using a medical ultrasound device at the frequency of 33 MHz. The results demonstrate the impact of microbubbles’ stabilization using gold nanoparticle/photodynamic dye hybrid structures to achieve probe applications in theranostics.

A near-infrared and lysosomal targeting thiophene-BODIPY photosensitizer: Synthesis and its imaging guided photodynamic therapy of cancer cells

In this study, a novel NIR and lysosomal targeting thiophene-BODIPY photosensitizer SBOP-Lyso was synthesized to explore its potential applications in photodynamic therapy of A549 cells. In the strategy of designing SBOP-Lyso, S atom in thiophene as well as heavy atom I were introduced to promote ISC efficiency to ensure high singlet oxygen yield. A common lysosome targeted group (M1: 1-(2-morpholinoethyl)-1H-indole-3-carbaldehyde) was linked to SBOP to extend its wavelength to the NIR region. Its absorption peak was at 660 nm (εmax = 5.2 × 104 cm−1 M−1) and its corresponding emission peak was located at 705 nm. Singlet oxygen could be quickly generated by SBOP-Lyso in the presence of 660 nm LED irradiation and the singlet oxygen yield was up to 44.1%. In addition, it also had good biocompatibility and could enter cells or zebrafish in a short time. SBOP-Lyso had negligible dark cytotoxicity (cell survival rate > 80%) and excellent phototoxicity (IC50 = 0.2 μM). DCFH-DA (ROS indicator) proved that SBOP-Lyso could generate singlet oxygen with 660 nm LED irradiation. Singlet oxygen produced by SBOP-Lyso could kill cancer cells in PDT process and it had the ability to effectively inhibit A549 cells migration. Besides that, lysosomal colocalization assay showed that it had good lysosomal localization ability (Pearson colocation coefficient, R = 0.93). Considering the above results, SBOP-Lyso as a unique lysosome-targeted photosensitizer with excellent properties would exhibit positive results in PDT process of cancer cells.

Comparative singlet oxygen photosensitizer efficiency of berberine, rose bengal, and methylene blue by time course nuclear magnetic resonance (NMR) monitoring of a photochemical 4+2 cycloaddition endoperoxide formation

Berberine, a natural product alkaloid, has been shown to exert biological activity via in situ production of singlet oxygen when photo irradiated. Berberine utilizes singlet oxygen in its putative mechanism of action, wherein it forms an activated complex with DNA and photosensitizes triplet oxygen to singlet oxygen to specifically oxidize guanine residues, thereby halting cell replication and leading to cell death. This has potential application in photodynamic therapy, alongside other such compounds which also act as photosensitizers and produce singlet oxygen in situ. The quantification of singlet oxygen in various photosensitizers, including berberine, is essential for determining their photosensitizer efficiencies. We postulated that the singlet oxygen produced by photoirradiation of berberine would be superior in terms of singlet oxygen production to the aforementioned photosensitizers when irradiated with UV light, but inferior under visible light conditions, due to its strong absorbance of UV wavelengths. Here, we report the usage of time course 1H nuclear magnetic resonance (NMR) spectroscopy to trap singlet oxygen via a 4+2 cycloaddition with terpinene, as well as theoretical calculations by time-dependent density functional theory (TD-DFT) towards quantification of berberine's singlet oxygen production against two known photosensitizers, methylene blue and rose bengal, to determine berberine’s efficacy as a singlet oxygen photosensitizer. We envision that similar processes can be utilized for the evaluation of berberine analogs or other photosensitizing agents and the identification of other potential medicinally significant singlet oxygen photosensitizers.

Development of Spirulina sea-weed raw extract/polyamidoamine hydrogel system as novel platform in photodynamic therapy: Photostability and photoactivity of chlorophyll a

The aim of this paper is to present and characterize Polyamidoamine-based hydrogels (PAA) as scaffolds to host photoactive Chlorophyll a (Chl a) from Spirulina (Arthrospira platensis) sea-weed Extract (SE), for potential applications in Photodynamic Therapy (PDT). The pigment extracted from SE was blended inside PAA without further purification, according to Green Chemistry principles. A comprehensive investigation of this hybrid platform, PAA/SE-based, was thus performed in our laboratory and, by means of Visible absorption and emission spectroscopies, the Chl a features, stability and photoactivity were studied. The obtained results evidenced the presence of two main Chl a forms, monomeric and dimeric, interacting with hydrogel polyamidoamines network. To better understand the nature of this interaction, the spectroscopic investigation of this system was performed both before and after the solidification of the hydrogel, that occurred at least in 24 h. Then, focusing the attention on solid scaffold, the 1Chl a⁎ fluorescence lifetime and FTIR-ATR analyses of PAA/SE were carried out, confirming the findings. The swelling and Point Zero Charge (PZC) measurements of solid PAA and PAA/SE were additionally performed to investigate the hydrogel behavior in water. Chl a molecules blended in PAA were (photo) stable and photoactive, and this latter feature was demonstrated showing that the pigment induced, when swelled in water and under irradiation, the formation of singlet oxygen (1O2), measured by direct and indirect methods.

Corroles and Hexaphyrins: Synthesis and Application in Cancer Photodynamic Therapy.

Corroles and hexaphyrins are porphyrinoids with great potential for diverse applications. Like porphyrins, many of their applications are based on their unique capability to interact with light, i.e., based on their photophysical properties. Corroles have intense absorptions in the low-energy region of the uv-vis, while hexaphyrins have the capability to absorb light in the near-infrared (NIR) region, presenting photophysical features which are complementary to those of porphyrins. Despite the increasing interest in corroles and hexaphyrins in recent years, the full potential of both classes of compounds, regarding biological applications, has been hampered by their challenging synthesis. Herein, recent developments in the synthesis of corroles and hexaphyrins are reviewed, highlighting their potential application in photodynamic therapy.

Two photoactive Ru (II) compounds based on tetrazole ligands for photodynamic therapy

Ru (II) compounds have potential application in photodynamic therapy (PDT). In the current study, two Ru (II) compounds based on the auxiliary ligand 2,2′-bipyridine (bipy) by changing main ligands 5-(2-pyridyl) tetrazole (Hpytz) and di(2H-tetrazol-5-yl) amine (H2datz) have been successfully synthesized and characterized, [Ru (pytz)(bipy)2][PF6] (1) and [Ru(Hdatz)(bipy)2][PF6] (2). These compounds can form nanoparticles (NPs) by nano-precipitation. And [Ru(pytz)(bipy)2][PF6] NPs with a lower half maximal inhibitory concentration (IC50) of 37 μg/mL on HeLa cells than that of [Ru(Hdatz)(bipy)2][PF6] NPs (65 μg/mL). Meanwhile, negligible dark toxicity has been also observed for these NPs even under high concentrations. The results show that [Ru(pytz)(bipy)2][PF6] (1) and [Ru(Hdatz)(bipy)2][PF6] (2) NPs can inhibit cell proliferation in vitro, and may be potential candidates for photodynamic therapy.

The investigation of unique water-soluble heptamethine cyanine dye for use as NIR photosensitizer in photodynamic therapy of cancer cells.

In this paper, a unique water-soluble heptamethine cyanine dye as NIR photosensitizer was synthesized to explore its properties associated with potential applications in photodynamic therapy (PDT). In the strategy of designing this photosensitizer, a sulfonic acid was used as a water soluble functional group and linked to the fluorophore through alkyl chains. 4-amino-2,2,6,6-tetramethylpiperidine-N-oxyl(Tempo) moiety was used as the a nitroxide spin label in obtaining biochemical reaction information in vivo due to it could greatly increase the inter-system crossing (ISC) process for triplet-state photosensitizers and low toxicity. As expected, the photosensitizers performed well in vitro photodynamic therapy. There were a remarkable absorbance band located at 692 nm and emission peaks falls at 762 nm, the quantum yield (Φf) was calculated to be 12.12% in pure aqueous solution using ICG as standards. The photosensitizer also has high singlet oxygen quantum yield (Φ△) for 16.96% with NIR LED irradiation. This photosensitizer can rapidly produce singlet oxygen and exhibit high phototoxicity under NIR light irradiation. It has excellent cellular uptake ability and better cell compatibility. It was also successfully applied in Near-infrared fluorescence imaging and AO/EB staining. In a whole, the organic dye based on Heptamethine cyanine used as photosensitizer has great potential in vivo cancer treatment.

Synthesis of Nanoparticles of ZnS:Ag-L-cysteine-protoporphyrin IX Conjugates and Investigation its Potential of Reactive Oxygen Species Production.

In this paper, L-cysteine capped Ag doped ZnS nanoparticles (NPs) were synthesized and its usage in photodynamic therapy was examined. Also, the details of the conjugation method for prepared NPs with sensitizer of protoporphyrin IX (PpIX) were reported. FT-IR studies indicate the formation of ZnS:Ag nanoparticles capped with L-cysteine and an amide-bond formation between PpIX and L-cysteine-capped ZnS:Ag NPs. The formation of ZnS:Ag NPs conjugated to protoporphyrin IX was confirmed through the use of SEM, TEM, UV-Visible, FT-IR and DLS analysis. The efficient energy transfer from ZnS:Ag to PpIX sensitizer was estimated at about 90%. The production of reactive oxygen species, including singlet oxygen and free radicals, from ZnS:Ag NPs conjugated to protoporphyrin IX, was observed using a chemical method. The production of reactive oxygen species of this conjugate indicates its potential application in photodynamic therapy.

Tetraphenylporphyrin intended for use in photodynamic therapy: Influence of sonophoresis and the formulation (solution or microemulsion) on percutaneous penetration

Tetraphenylporphyrin (H2TPP), was synthesized and characterized by UV and FTIR spectroscopy. H2TPP was included in a solution (Labrasol™:Transcutol™ 1:2 v/v) and in a microemulsion (whose composition was chosen from the construction of pseudo-ternary diagrams). Permeation experiments were performed with these two systems through intact skin and skin pretreated with sonophoresis. Confocal laser scanning microscopy was useful to evidence that in all cases, H2TPP penetrated the interior of the skin, increasing the amount that penetrates when the skin was treated with sonophoresis, especially for the combination sonophoresis/microemulsion, with which the highest permeated amount was achieved. In no case, H2TPP was found in the receptor medium, which may be desirable if the aim is to reduce a systemic effect. The results obtained suggest that the proposed systems have potential application in photodynamic therapy, whose effectiveness depends on the penetration and accumulation of photosensitizer in the affected tissue.

Photodynamic Activity of Vitamin-Chlorin Conjugates at Nanomolar Concentrations against Triple-Negative Breast Cancer Cells

The synthesis and characterization of chlorin-based photosensitizers for potential applications in photodynamic therapy (PDT) of triple-negative breast cancer are described. The photodynamic efficacies of the synthesized chlorin-bexarotene (CBX) and its zinc and indium complexes were compared to those of the previously synthesized chlorin-biotin conjugates in triple-negative and triple-positive breast cancer cell lines. The chlorin-bexarotene (CBX) and chlorin-biotin (CBTN) aim to target the nuclear receptors and vitamin receptors, respectively, upregulated in malignant cancer cells. Cell survival assay in vitro indicated that the biotinylated chlorin is photoactive at the nanomolar concentration range against triple-negative breast cancer cell line, but has some dark toxicity at higher concentrations, while chlorin-bexarotene is photoactive at the nanomolar range at higher light dose with no observable dark toxicity at the highest concentration used. With the proper adjustment of concentration and light ...

Blue Copper Peroxidase and Phthalocyanine Conjugate: Synthesis, Characterization, and Applications.

Trametes versicolor can degrade bark as a source for carbon necessity. Therefore, it secretes lignin peroxidase, mangan peroxidase, and laccase. The laccase enzyme was produced in high yield at pH of 5 and glucose concentration of 10 g L-1. In optimized medium, the enzyme activity was between 200 and 250 U L-1 when an inducer was absent. It was seen that the activity reached 400 U L-1 when phenol was used as an inducer. The molecular weight of purified laccase was found to be 80 kDa with SDS-PAGE, and kinetic constant Km and Vmax values for 2,2'-azino-bis(3-ethylbenzthiazoline)-6-sulfonate were determined to be 3.66 × 10-4 μM and 1652 U L-1, respectively. Because of these properties, these enzymes are widely used, free or immobilized, in industrial areas. Laccase enzyme decolorization of six different dyes was carried out. A decolorization capacity of 50-99% was achieved by cultivation for 20 days using a beginning dye concentration of 20 ppm. The removal of color with an active enzyme was obtained around 90%. Also, the laccase enzyme was conjugated, amine-functionalized, low-symmetry phthalocyanine. This conjugate was examined by both photodynamic therapy and chemosensor application. This conjugate fluorescence had a quantum yield of 0.32 (lifetime 3.59 ns) and efficiently generated singlet oxygen (quantum yield 0.4). The conjugate successfully displayed photodamage in HeLa and HuH-7 cells in the photodynamic therapy application. These results indicate that the conjugate represents an interesting agent with potential applications in photodynamic therapy. In addition, the chemosensor behavior of this compound to different metal ions has been studied, and this conjugate is displayed as a fluorescence chemosensor for the determination of Fe3+ions.

Rapid one-pot synthesis of pyrrole-appended isocorroles.

Free-base meso-triarylcorroles have been found to undergo oxidative coupling with an excess of pyrrole in dichloromethane in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) affording 5/10-pyrrole-appended isocorroles in reasonable yields (35-60%) and in a matter of seconds. The free-base isocorrole ligands could all be complexed to copper with Cu(OAc)2·H2O in chloroform/methanol in 55-80% yields. Single-crystal X-ray structures of two of the new compounds (H2[5-pyr-TpOMePiC] and Cu[10-pyr-TpOMePiC]) revealed planar macrocycles with rms atomic displacements of only 0.02 and 0.06 Å relative to their respective best-fit C19N4 planes. Both free-base and Cu(ii)-complexed isocorroles exhibit richly featured UV-vis-NIR spectra with red/NIR absorption maxima at ∼650 nm and ∼725 nm for the free-bases and ∼800-850 nm for the copper complexes, suggesting potential applications in photodynamic therapy. Cyclic voltammetric analyses of five of the Cu complexes revealed fully reversible redox cycles with multiple oxidation and reduction features.

Porphyrin-functionalized coordination star polymers and their potential applications in photodynamic therapy

We present a new family of porphyrin-functionalized coordination star polymers prepared through combination of coordination-driven self-assembly and post-assembly polymerization. Their self-assembly behaviour in water and potential for photodynamic therapy were demonstrated.

Silk fibroin hydrogels for potential applications in photodynamic therapy.

In this study, we prepared translucid hydrogels with different concentrations of silk fibroin, extracted from raw silk fibers, and used them as a matrix to incorporate the photosensitizer 5-(4-aminophenyl)-10,15,20-tris-(4-sulphonatophenyl) porphyrin trisodium for application in photodynamic therapy (PDT). The hydrogels obtained were characterized by rheology, spectrophotometry, and scattering techniques to elucidate the factors involved in the formation of the hydrogel, and to characterize the behavior of silk fibroin (SF) after incorporating of the porphyrin to the matrix. The rheology results demonstrated that the SF hydrogels had a shear thinning behavior. In addition, we were able to verify that the structure of the material was able to be recovered over time after shear deformation. The encapsulation of porphyrins in hydrogels leads to the formation of self-assembled peptide nanostructures that prevent porphyrin aggregation, thereby greatly increasing the generation of singlet oxygen. Also, our findings suggest that porphyrin can diffuse out of the hydrogel and permeate the outer skin layers. This evidence suggests that SF hydrogels could be used as porphyrin encapsulation and as a drug carrier for the sustained release of photosensitizers for PDT.

The Structures, Spectroscopic Properties, and Photodynamic Reactions of Three [RuCl(QN)NO]- Complexes (HQN = 8-Hydroxyquinoline and Its Derivatives) as Potential NO-Donating Drugs.

The structures and spectral properties of three ruthenium complexes with 8-hydroxyquinoline (Hhqn) and their derivatives 2-methyl-8-quinolinoline (H2mqn) and 2-chloro-8-quiolinoline (H2cqn) as ligands (QN = hqn, 2mqn, or 2cqn) were calculated with density functional theory (DFT) at the B3LYP level. The UV-Vis and IR spectra of the three [RuCl(QN)NO]− complexes were theoretically assigned via DFT calculations. The calculated spectra reasonably correspond to the experimentally measured spectra. Photoinduced NO release was confirmed through spin trapping of the electron paramagnetic resonance spectroscopy (EPR), and the dynamic process of the NO dissociation upon photoirradiation was monitored using time-resolved infrared (IR) spectroscopy. Moreover, the energy levels and related components of frontier orbitals were further analyzed to understand the electronic effects of the substituent groups at the 2nd position of the ligands on their photochemical reactivity. This study provides the basis for the design of NO donors with potential applications in photodynamic therapy.

Bisarylselanylbenzo‐2,1,3‐selenadiazoles: Synthesis, Photophysical, Electrochemical and Singlet‐Oxygen‐Generation Properties

We describe herein our results on the synthesis of bisarylselanylbenzo‐2,1,3‐selenadiazoles through double cross‐coupling reaction. The named compounds were obtained in moderate to good yields by reactions of a range of diaryl diselenides with the 4,7‐dibromobenzo[c][1,2,5]selenadiazole using 20 mol‐% of CuO nanoparticles as a catalyst. In addition, the obtained compounds were investigated regarding their photophysical properties in solution and singlet oxygen generation. Bisarylselanylbenzo‐2,1,3‐selenadiazoles presents strong absorption bands at UV region and red emission properties, depending on the substituent. Geometrical, photophysical and electronic properties of the compounds are characterized with density functional theory calculations. In all derivatives are observed the oxidation process of Se atom, using electrochemical analysis. Also, the quantum yields of photosensitized 1O2 production of the synthesized compounds were slightly lower than the standard, but still displays good ability to generate singlet oxygen species. The ability to generate 1O2 of benzo‐2,1,3‐selenadiazole derivatives after being exposed to light and oxygen allowed us to envisage them as a potential application in photodynamic therapy.

Optimized Heptamethine Cyanines for Photodynamic Therapy.

Over 10 near-IR fluorescent sensitizers were prepared to explore their properties relevant to potential applications in photodynamic therapy (PDT). Key properties of these compounds are that they can be excited around 800 nm, (i) are hydrophilic, (ii) generate singlet oxygen with acceptable quantum yields, and (iii) are imported into cancer cells via the organic anion transporter proteins (OATPs). (This is crucial to tumor localization.) The N-substituents of these cyanines were varied to adjust their charges and polarities and to accommodate conjugation to other entities (e.g., biomolecules or fragments to expand their theranostic modalities). Thus, it was possible to optimize their photocytotoxicities without compromising their other desirable characteristics for PDT. Overall, sensitizers like this have superior characteristics relative to clinically approved sensitizers for PDT insofar as they can be excited at greater depths in tissue.