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1.
Singlet oxygen (1O2) is the primary oxidant generated in photodynamic therapy (PDT) protocols involving sensitizers resulting in type II reactions. 1O2 can give rise to additional reactive oxygen species (ROS) such as the hydroxyl radical (?OH). The current study was designed to assess 3′‐p‐(aminophenyl) fluorescein (APF) and 3′‐p‐(hydroxyphenyl) fluorescein (HPF) as probes for the detection of 1O2 and ?OH under conditions relevant to PDT. Cell‐free studies indicated that both APF and HPF were converted to fluorescent products following exposure to 1O2 generated by irradiation of a water‐soluble photosensitizing agent (TPPS) and that APF was 35‐fold more sensitive than HPF. Using the 1O2 probe singlet oxygen sensor green (SOSG) we confirmed that 1 mm NaN3 quenched 1O2‐induced APF/HPF fluorescence, while 1% DMSO had no effect. APF and HPF also yielded a fluorescent product upon interacting with ?OH generated from H2O2 via the Fenton reaction in a cell‐free system. DMSO quenched the fluorogenic interaction between APF/HPF and ?OH at doses as low as 0.02%. Although NaN3 was expected to quench ?OH‐induced APF/HPF fluorescence, co‐incubating NaN3 with APF or HPF in the presence of ?OH markedly enhanced fluorescence. Cultured L1210 cells that had been photosensitized with benzoporphyhrin derivative exhibited APF fluorescence immediately following irradiation. Approximately 50% of the cellular fluorescence could be suppressed by inclusion of either DMSO or the iron‐chelator desferroxamine. Combining the latter two agents did not enhance suppression. We conclude that APF can be used to monitor the formation of both 1O2 and ?OH in cells subjected to PDT if studies are performed in the presence and absence of DMSO, respectively. That portion of the fluorescence quenched by DMSO will represent the contribution of ?OH. This procedure could represent a useful means for evaluating formation of both ROS in the context of PDT.  相似文献   

2.
Sustained tumor oxygenation is of critical importance during type‐II photodynamic therapy (PDT), which depends on the intratumoral oxygen level for the generation of reactive oxygen species. Herein, the modification of photosynthetic cyanobacteria with the photosensitizer chlorin e6 (ce6) to form ce6‐integrated photosensitive cells, termed ceCyan, is reported. Upon 660 nm laser irradiation, sustained photosynthetic O2 evolution by the cyanobacteria and the immediate generation of reactive singlet oxygen species (1O2) by the integrated photosensitizer could be almost simultaneously achieved for tumor therapy using type‐II PDT both in vitro and in vivo. This work contributes a conceptual while practical paradigm for biocompatible and effective PDT using hybrid microorganisms, displaying a bright future in clinical PDT by microbiotic nanomedicine.  相似文献   

3.
This preclinical study examines light fluence, photodynamic therapy (PDT) dose and “apparent reacted singlet oxygen,” [1O2]rx, to predict local control rate (LCR) for Photofrin‐mediated PDT of radiation‐induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in‐air fluences (50–250 J cm?2) and in‐air fluence rates (50–150 mW cm?2) at Photofrin dosages of 5 and 15 mg kg?1 and a drug‐light interval of 24 h using a 630‐nm, 1‐cm‐diameter collimated laser. A macroscopic model was used to calculate [1O2]rx and PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [1O2]rx were defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [1O2]rx ≥ 1.1 mm or PDT dose ≥1200 μm J cm?2 but cannot be predicted with fluence alone. LCR increases with increasing [1O2]rx and PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [1O2]rx outperformed both PDT dose and fluence in predicting tumor response and correlating with LCR.  相似文献   

4.
Development of a photosensitizing system that can reversibly control the generation of singlet oxygen (1O2) is of great interest for photodynamic therapy (PDT). Recently several photosensitizer–photochromic‐switch dyads were reported as a potential means of the 1O2 control in PDT. However, the delivery of such a homogeneous molecular dyad as designed (e.g., optimal molar ratio) is extremely challenging in living systems. Herein we show a Zr‐MOF nanoplatform, demonstrating energy transfer‐based 1O2 controlled PDT. Our strategy allows for tuning the ratios between photosensitizer and the switch molecule, enabling maximum control of 1O2 generation. Meanwhile, the MOF provides proximal placement of the functional entities for efficient intermolecular energy transfer. As a result, the MOF nanoparticle formulation showed enhanced PDT efficacy with superior 1O2 control compared to that of homogeneous molecular analogues.  相似文献   

5.
A biocompatible fluorescent nanoprobe for singlet oxygen (1O2) detection in biological systems was designed, synthesized, and characterized, that circumvents many of the limitations of the molecular probe Singlet Oxygen Sensor Green® (SOSG). This widely used commercial singlet oxygen probe was covalently linked to a polyacrylamide nanoparticle core using different architectures to optimize the response to 1O2. In contrast to its molecular counterpart, the optimum SOSG‐based nanoprobe, which we call NanoSOSG, is readily internalized by E. coli cells and does not interact with bovine serum albumin. Furthermore, the spectral characteristics do not change inside cells, and the probe responds to intracellularly generated 1O2 with an increase in fluorescence.  相似文献   

6.
Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non‐selective release of photosensitizers still exist. Herein, we report a 1O2‐responsive block copolymer (POEGMA‐b‐P(MAA‐co‐VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen (1O2) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The 1O2‐responsiveness of POEGMA‐b‐P(MAA‐co‐VSPpaMA) block copolymer enabled the realization of self‐amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT.  相似文献   

7.
Currently, photosensitizers (PSs) that are microenvironment responsive and hypoxia active are scarcely available and urgently desired for antitumor photodynamic therapy (PDT). Presented herein is the design of a redox stimuli activatable metal‐free photosensitizer (aPS), also functioning as a pre‐photosensitizer as it is converted to a PS by the mutual presence of glutathione (GSH) and hydrogen peroxide (H2O2) with high specificity on a basis of domino reactions on the benzothiadiazole ring. Superior to traditional PSs, the activated aPS contributed to efficient generation of reactive oxygen species including singlet oxygen and superoxide ion through both type 1 and type 2 pathways, alleviating the aerobic requirement for PDT. Equipped with a triphenylphosphine ligand for mitochondria targeting, mito aPS showed excellent phototoxicity to tumor cells with low light fluence under both normoxic and hypoxic conditions, after activation by intracellular GSH and H2O2. The mito aPS was also compatible to near infrared PDT with two photon excitation (800 nm) for extensive bioapplications.  相似文献   

8.
Photodynamic therapy (PDT) is a promising new treatment technique which can potentially destroy unwanted and malignant tissues, such as those of cancer. The photodynamic mechanisms of three tetrapyrrole compounds: Mg‐purpurin‐18, tetra(meso‐chlorophenyl)porphyrin (m‐TCPP) and 2,7,12,18‐tetramethyl‐3,8‐di[(1‐isobutoxyl)‐ ethyl]‐13,17‐bis[3‐di(2‐chloroethyl)aminopropyl]porphyrin (TDBP) in acetonitrile were investigated by 355 nm laser flash photolysis. It was found that after laser flash photolysis (LFP), the excited states of TDBP and Mg‐purpurin‐18 could react with O2 and 1O2 was produced, which proved that TDBP and Mg‐purpurin‐18 took effects through type II mechanism in PDT. This suggested that TDBP and Mg‐purpurin‐18 should be suitable for target tissues containing enough O2. Mg‐purpurin‐18 has two extra absorptions at 550 and 700 nm, which means it has broad choices of laser wavelength in PDT. It was also found that m‐TCPP could be photoionized when excited with 355 nm laser under N2‐saturated condition. It could also react with O2 to produce reactive oxygen species such as superoxide and the peroxide anions, but not 1O2. These were known as the Type I mechanism. So m‐TCPP could be used even at low oxygen concentration or more polar environments with good behavior in PDT. From the above studies on the three different tetrapyrrole compounds it could be concluded that the structure of porphin ring takes a main role in PDT. And there was important impact on the photodynamic mechanism for the functional group directly connecting with porphin ring, while little influence for the functional group indirectly connecting with porphin ring. These will be of great value in the discovery of new PDT drugs.  相似文献   

9.
A technique is introduced that monitors the depletion of intracellular ground state oxygen concentration ([3O2]) during photodynamic therapy of Mat‐LyLu cell monolayers and cell suspensions. The photosensitizer Pd(II) meso‐tetra(4‐carboxyphenyl)porphine (PdT790) is used to manipulate and indicate intracellular [3O2] in both of the in vitro models. The Stern–Volmer relationship for PdT790 phosphorescence was characterized in suspensions by flowing nitrogen over the suspension while short pulses of 405 nm light were used to excite the sensitizer. The bleaching of sensitizer and the oxygen consumption rate were also measured during continuous exposure of the cell suspension to the 405 nm laser. Photodynamic therapy (PDT) was conducted in both cell suspensions and in cell monolayers under different treatment conditions while the phosphorescence signal was acquired. The intracellular [3O2] during PDT was calculated by using the measured Stern–Volmer relationship and correcting for sensitizer photobleaching. In addition, the amount of oxygen that was consumed during the treatments was calculated. It was found that even at large oxygen consumption rates, cells remain well oxygenated during PDT of cell suspensions. For monolayer treatments, it was found that intracellular [3O2] is rapidly depleted over the course of PDT.  相似文献   

10.
Traditional photodynamic therapy (PDT) is dependent on externally applied light and oxygen, and the depth of penetration of these factors can be insufficient for the treatment of deep infections. The short half-life and short diffusion distance of reactive oxygen species (ROS) also limit the antibacterial efficiency of PDT. Herein, we designed a targeting singlet oxygen delivery system, CARG-Py, for irradiation-free and oxygen-free PDT. This system was converted to the “singlet oxygen battery” CARG-1O2 and released singlet oxygen without external irradiation or oxygen. CARG-1O2 is composed of pyridones coupled to a targeting peptide that improves the utilization of singlet oxygen in deep multidrug-resistant bacterial infections. CARG-1O2 was shown to damage DNA, protein, and membranes by increasing the level of reactive oxygen inside bacteria; the attacking of multiple biomolecular sites caused the death of methicillin-resistant Staphylococcus aureus (MRSA). An in vivo study in a MRSA-infected mouse model of pneumonia demonstrated the potential of CARG-1O2 for the efficient treatment of deep infections. This work provides a new strategy to improve traditional PDT for irradiation- and oxygen-free treatment of deep infections while improving convenience of PDT.  相似文献   

11.
When irradiated, fullerene efficiently generates reactive oxygen species (ROS) and is an attractive photosensitizer for photodynamic therapy (PDT). Ideally, photosensitizers for PDT should be water-soluble and tumor-specific. Because cancer cells endocytose glucose more effectively than normal cells, the characteristics of fullerene as a photosensitizer were improved by combining it with glucose. The cytotoxicity of PDT was studied in several cancer cell lines cultured with C60-(Glc)1 (d -glucose residue pendant fullerene) and C60-(6Glc)1 (a maltohexaose residue pendant fullerene) subsequently irradiated with UVA1. PDT alone induced significant cytotoxicity. In contrast, PDT with the glycoconjugated fullerene exhibited no significant cytotoxicity against normal fibroblasts, indicating that PDT with these compounds targeted cancer cells. To investigate whether the effects of PDT with glycoconjugated fullerene were because of the generation of singlet oxygen (1O2), NaN3 was added to cancer cells during irradiation. NaN3 extensively blocked PDT-induced apoptosis, suggesting that PDT-induced cell death was a result of the generation of 1O2. Finally, to investigate the effect of PDT in vivo, melanoma-bearing mice were injected intratumorally with C60-(Glc)1 and irradiated with UVA1. PDT with C60-(Glc)1 suppressed tumor growth. These findings indicate that PDT with glycoconjugated fullerene exhibits tumor-specific cytotoxicity both in vivo and in vitro via the induction of 1O2.  相似文献   

12.
Novel methods for the determination of polyphenolic antioxidants present in extracts from inflorescences of Cirsium vulgare (Savi) Ten. based on ultra‐high performance liquid chromatography with photodiode array and chemiluminescence detection have been developed. Under the optimized conditions of chromatographic separation the analytical characteristic of the method was performed. The proposed method was successfully applied to the determination of ten polyphenols present in inflorescences of Cirsium vulgare . A comparison of the contents of analytes in extracts prepared by using various extraction media (methanol, ethanol, 70% methanol, 70% ethanol, and water) was carried out for the first time. For the postcolumn detection of scavenging activity of polyphenolic antioxidants against reactive oxygen species (H2O2, OH, O2• −) three systems based on chemiluminescence of luminol were used. A review of the current scientific literature shows that this is the first report on the application of luminol‐based postcolumn detection for the on‐line investigation of OH scavenging activity. The main compound determined in extracts from inflorescences of Cirsium vulgare was apigenin 7‐O‐glucuronide, whereas the highest antioxidant activity was observed for chlorogenic acid, luteolin 7‐O‐glucoside, and apigenin.  相似文献   

13.
Sustained tumor oxygenation is of critical importance during type-II photodynamic therapy (PDT), which depends on the intratumoral oxygen level for the generation of reactive oxygen species. Herein, the modification of photosynthetic cyanobacteria with the photosensitizer chlorin e6 (ce6) to form ce6-integrated photosensitive cells, termed ceCyan, is reported. Upon 660 nm laser irradiation, sustained photosynthetic O2 evolution by the cyanobacteria and the immediate generation of reactive singlet oxygen species (1O2) by the integrated photosensitizer could be almost simultaneously achieved for tumor therapy using type-II PDT both in vitro and in vivo. This work contributes a conceptual while practical paradigm for biocompatible and effective PDT using hybrid microorganisms, displaying a bright future in clinical PDT by microbiotic nanomedicine.  相似文献   

14.
Continuous irradiation during photodynamic therapy (PDT) inevitably induces tumor hypoxia, thereby weakening the PDT effect. In PDT‐induced hypoxia, providing singlet oxygen from stored chemical energy may enhance the cell‐killing effect and boost the therapeutic effect. Herein, we present a phototheranostic (DPPTPE@PEG‐Py NPs) prepared by using a 2‐pyridone‐based diblock polymer (PEG‐Py) to encapsulate a semiconducting, heavy‐atom‐free pyrrolopyrrolidone‐tetraphenylethylene (DPPTPE) with high singlet‐oxygen‐generation ability both in dichloromethane and water. The PEG‐Py can trap the 1O2 generated from DPPTPE under laser irradiation and form a stable intermediate of endoperoxide, which can then release 1O2 in the dark, hypoxic tumor microenvironment. Furthermore, fluorescence‐imaging‐guided phototherapy demonstrates that this phototheranostic could completely inhibit tumor growth with the help of laser irradiation.  相似文献   

15.
A novel N‐borylbenzyloxycarbonyl‐3,7‐dihydroxyphenoxazine fluorescent probe (NBCD) for detecting H2O2 in living cells is described. The probe could achieve high selectivity for detecting H2O2 over other biological reactive oxygen species (ROS). In addition, upon addition of H2O2, NBCD exhibited color change from colorless to pink, which makes it a “naked‐eye” probe for H2O2 detection. NBCD could not only be used to detect enzymatically generated H2O2 but also to detect H2O2 in living systems by using fluorescence spectroscopy, with a detection limit of 2 μm . Importantly, NBCD enabled the visualization of epidermal growth factor (EGF)‐stimulated H2O2 generation inside the cells.  相似文献   

16.
Image-guided photodynamic therapy (PDT) has received growing attention due to its non-invasiveness and precise controllability. However, the PDT efficiency of most photosensitizers are decreased in living system due to the aggregation-caused singlet oxygen (1O2) generation decreasing. Herein, we present an Iridium (III) pyridylpyrrole complex (Ir-1) featuring of aggregation-induced emission (AIE) and 1O2 generation characteristics for image-guided PDT of cancer. Ir-1 aqueous solution exhibits bright red phosphorescence peaked at 630 nm, large Stokes shift of 227 nm, and good 1O2 generation ability. The 1O2 generating rate of Ir-1 in EtOH/water mixture solution is 2.3 times higher than that of Rose Bengal. In vitro experimental results revealed that Ir-1 has better biocompatibility and higher phototoxicity compared with clinically used photosensitizers (Rose Bengal and Ce6), suggesting that Ir-1 can serve as a photosensitizer for image-guided PDT of cancer.  相似文献   

17.
Inflammatory cells, most especially neutrophils, can be a necessary component of the antitumor activity occurring after administration of photodynamic therapy. Generation of neutrophil responses has been suggested to be particularly important in instances when the delivered photodynamic therapy (PDT) dose is insufficient. In these cases, the release of neutrophil granules and engagement of antitumor immunity may play an important role in eliminating residual disease. Herein, we utilize in vivo imaging of luminol chemiluminescence to noninvasively monitor neutrophil activation after PDT administration. Studies were performed in the AB12 murine model of mesothelioma, treated with Photofrin‐PDT. Luminol‐generated chemiluminescence increased transiently 1 h after PDT, followed by a subsequent decrease at 4 h after PDT. The production of luminol signal was not associated with the influx of Ly6G+ cells, but was related to oxidative burst, as an indicator of neutrophil function. Most importantly, greater levels of luminol chemiluminescence 1 h after PDT were prognostic of a complete response at 90 days after PDT. Taken together, this research supports an important role for early activity by Ly6G+ cells in the generation of long‐term PDT responses in mesothelioma, and it points to luminol chemiluminescence as a potentially useful approach for preclinical monitoring of neutrophil activation by PDT.  相似文献   

18.
Sensing of intracellular singlet oxygen (1O2) is required in order to optimize photodynamic therapy (PDT). An optical nanoprobe is reported here for the optical determination of intracellular 1O2. The probe consists of a porous particle core doped with the commercial 1O2 probe 1,3-diphenylisobenzofuran (DPBF) and a layer of poly-L-lysine. The nanoparticle probes have a particle size of ~80 nm in diameter, exhibit good biocompatibility, improved photostability and high sensitivity for 1O2 in both absorbance (peak at 420 nm) and fluorescence (with excitation/emission peaks at 405/458 nm). Nanoprobes doped with 20% of DPBF are best suited even though they suffer from concentration quenching of fluorescence. In comparison with the commercial fluorescent 1O2 probe SOSG, 20%-doped DPBF-NPs (aged) shows higher sensitivity for 1O2 generated at an early stage. The best nanoprobes were used to real-time monitor the PDT-triggered generation of 1O2 inside live cells, and the generation rate is found to depend on the supply of intracellular oxygen.
Graphical abstract A fluorescent nanoprobe featured with refined selectivity and improved sensitivity towards 1O2 was prepared from the absorption-based probe DBPF and used to real-time monitoring of the generation of intracellular 1O2 produced during PDT.
  相似文献   

19.
In this account, the reactive oxygen species (ROS) in photodynamic therapy (PDT) were deliberately reviewed. First, the specific definition of ROS and PDT were readily clarified. Afterward, this review focuses on the fundamental principles and applications of PDT. Due to strong oxidation ability of radicals (e.g., •OH and O2•-) and non-radical (e.g., 1O2 and H2O2), these ROS would attack the in vitro and in vivo tumor cells, thus achieving the goal of cancer treatment. Then, ROS in PDT for cancer treatment was thoroughly reviewed, including the mechanism and photosensitizer (PS) selection (i.e., nanomaterials). Ultimately, emphasis was made on the challenges, research gap, and prospects of ROS in cancer treatment and critically discussed. Hopefully, this review can offer detailed theoretical guidance for the researchers who participate in the study regarding ROS in PDT.  相似文献   

20.
Owing to their unique, nanoscale related optical properties, nanostructures assembled from molecular photosensitizers (PSs) have interesting applications in phototheranostics. However, most nanostructured PS assemblies are super‐quenched, thus, preventing their use in photodynamic therapy (PDT). Although some of these materials undergo stimuli‐responsive disassembly, which leads to partial recovery of PDT activity, their therapeutic potentials are unsatisfactory owing to a limited ability to promote generation reactive oxygen species (ROS), especially via type I photoreactions (i.e., not by 1O2 generation). Herein we demonstrate that a new, nanostructured phthalocyanine assembly, NanoPcA, has the ability to promote highly efficient ROS generation via the type I mechanism. The results of antibacterial studies demonstrate that NanoPcA has potential PDT applications.  相似文献   

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