Photodynamic Agents with Anti-metastatic Activities

Vummidi, Balayeshwanth R.; Noreen, Faiza; Alzeer, Jawad; Moelling, Karin; Luedtke, Nathan W.

doi:10.1021/cb400008t

Cited by 30 publications

(21 citation statements)

References 56 publications

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“…It is also evident the differences in the ABMA uorescence decay between the samples containing the porphyrins without metal (ATPP-LA 1 and ATPP-LA) and those with the porphyrin containing zinc in their core. This difference is associated to the presence of the zinc metal in the porphyrin molecule, which increases the capacity of the photosensitizer to generate singlet oxygen, as reported in the literature, 12,68,69 making this metalloporphyrin a promising PS for PDT. Finally, in order to compare the singlet oxygen production capacity of the free porphyrins (ATPP-LA 1 , ATPP-LA and ZnATPP-LA) and of the porphyrins loaded in the GNP (ATPP-LA-GNP and ZnATPP-LA-GNP), the maximum rate of ABMA photobleaching was normalized with the concentration of the PS using eqn (1), where IF is the intensity of uorescence.…”

Section: Singlet Oxygen Production Quanticationmentioning

confidence: 84%

Nanostructured materials for photodynamic therapy: synthesis, characterization and in vitro activity

et al. 2017

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Three nanostructured vehicles are proposed as potential carriers for photosensitizers to be used in photodynamic therapy: spherical nanoparticles, hexahedral microparticles and cylindrical magnetic nanorods. A comparative study of their photodynamic properties was performed, and the influence of their size and the amount of loaded porphyrin was considered to discuss their effects in the observed photodynamic activity. All the vehicles have a gold surface, allowing functionalization with a disulfide-containing porphyrin as the photosensitizer, as well as with a PEG-containing thiol to improve their biocompatibility and water solubility. The activity of the porphyrin loaded in each vehicle was assessed through in vitro photocytotoxicity studies using HeLa cells. A synergic effect for the porphyrin toxicity was observed in all of the vehicles. The zinc-containing porphyrin showed better production of singlet oxygen, and proved more photocytotoxic both in solution and loaded in any of the vehicles. The magnetism of the nanorods allows targeting with a magnetic field, but causes their aggregation, hampering the porphyrin's activity. Microparticles showed lower cell internalization but their bigger size allowed a high porphyrin loading, which translated into high photocytotoxicity. The highest cell internalization and photocytotoxicity was observed for the porphyrin-loaded nanoparticles, suggesting that a smaller size is favored in cell uptake

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Section: Singlet Oxygen Production Quanticationmentioning

confidence: 84%

Nanostructured materials for photodynamic therapy: synthesis, characterization and in vitro activity

et al. 2017

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“…Relevant to the CCK2R agonistic activity of SALPC (AlPcS 4 ) and AlPcS 2 , tetrakis-(di-isopropyl -guanidino) zinc phthalocyanine (Zn-DIGP), a phthalocyanine molecule with a central conjugated Zn 2+ , has recently been found to be an antagonist against the calcium-mobilizing G-protein-coupled receptor CXCR3, but at higher concentrations (IC 50 of 3.8 µM) [51]. In the case of Zn-DIGP, its peripheral hydrophilic di-isopropyl-guanidino groups have been found to be essential to its dark antagonistic activity, but the central conjugated zinc was found not to be essential.…”

Section: Discussionmentioning

confidence: 99%

“…In the case of Zn-DIGP, its peripheral hydrophilic di-isopropyl-guanidino groups have been found to be essential to its dark antagonistic activity, but the central conjugated zinc was found not to be essential. Instead, the removal of central conjugated Zn 2+ rather drastically enhanced its dark antagonist activity [51]. Interestingly, in a separate report, it was found that a completely water-insoluble gallium-conjugated phthalocyanine without any peripheral substitutions (GaPc) could be bound and dissolved by the bacterial heme acquisition system (Has) protein A (HasA) transported via HasA receptors into Pseudomonas aeruginosa bacterial cells for subsequent photodynamic inactivation [52].…”

Section: Discussionmentioning

confidence: 99%

Permanent Photodynamic Activation of the Cholecystokinin 2 Receptor

Tang

Cui

2020

Biomolecules

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The cholecystokinin 2 receptor (CCK2R) is expressed in the central nervous system and peripheral tissues, playing an important role in higher nervous and gastrointestinal functions, pain sensation, and cancer growth. CCK2R is reversibly activated by cholecystokinin or gastrin, but whether it can be activated permanently is not known. In this work, we found that CCK2R expressed ectopically in CHO-K1 cells was permanently activated in the dark by sulfonated aluminum phthalocyanine (SALPC/AlPcS4, 10–1000 nM), as monitored by Fura-2 fluorescent calcium imaging. Permanent CCK2R activation was also observed with AlPcS2, but not PcS4. CCK2R previously exposed to SALPC (3 and 10 nM) was sensitized by subsequent light irradiation (>580 nm, 31.5 mW·cm−2). After the genetically encoded protein photosensitizer mini singlet oxygen generator (miniSOG) was fused to the N-terminus of CCK2R and expressed in CHO-K1 cells, light irradiation (450 nm, 85 mW·cm−2) activated in-frame CCK2R (miniSOG-CCK2R), permanently triggering persistent calcium oscillations blocked by the CCK2R antagonist YM 022 (30 nM). From these data, it is concluded that SALPC is a long-lasting CCK2R agonist in the dark, and CCK2R is photogenetically activated permanently with miniSOG as photosensitizer. These properties of SALPC and CCK2R could be used to study CCK2R physiology and possibly for pain and cancer therapies.

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“…It is based on photosensitizers and laser light with a specific wavelength, causing the production of reactive oxygen species (ROS) and inducing tumor cell apoptosis/necrosis (16). PDT has been clinically used for various cancers, including cervical (17), lung(18), bladder (19), skin (20) and head and neck cancers (5,21).…”

Section: Introductionmentioning

confidence: 99%

MPPa-PDT suppresses breast tumor migration/invasion by inhibiting AKT-NF-κB-dependent MMP-9 expression via ROS

Huang

Lin

Chen

et al. 2019

Preprint

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Background: Breast cancer is one of the most commonly diagnosed cancers in women, with high morbidity and mortality. Tumor metastasis is implicated in most breast cancer deaths; thus, inhibiting metastasis may provide a therapeutic direction for breast cancer. In the present study, pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) was used to inhibit metastasis in MCF-7 breast cancer cells. Methods: Uptake of MPPa was detected by fluorescence microscopy. Cell viability was evaluated by the Cell Counting Kit-8 (CCK-8). ROS generation was detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The migration of cells was assessed by wound healing assay, and invasion ability was assessed by Matrigel invasion assay. Levels of MMP2 and MMP9 were measured by PCR. Akt, phospho-Akt (Ser473), phospho-NF-κB p65 (Ser536) and NF-κB p65 were measured by western blotting. The F-actin cytoskeleton was observed by immunofluorescence. Lung tissue was visualized by hematoxylin and eosin staining. Results: Following MPPa-PDT, migration and invasion were decreased in the MCF-7 cells. MPPa-PDT downregulated the expression of MMP2 and MMP9, which are responsible for the initiation of metastasis. MPPa-PDT reduced the phosphorylation of Akt and NF-κB. MPPa-PDT also reduced and destroyed the F-actin cytoskeleton in MCF-7 cells. These effects were blocked by the reactive oxygen species scavenger NAC or the Akt activator SC79, while the PI3K inhibitor LY294002 or the Akt inhibitor triciribine enhanced these effects. Moreover, MPPa-PDT inhibited tumor metastasis and destroyed F-actin in vivo. Conclusion: Taken together, these results demonstrate that MPPa-PDT inhibits the metastasis of MCF-7 cells both in vitro and in vivo and may be involved in the Akt/NF-κB-dependent MMP-9 signaling pathway. Thus, MPPa-PDT may be a promising treatment to inhibit metastasis. Key words: photodynamic therapy, reactive oxygen species, breast tumor, migration, invasion

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Photodynamic Agents with Anti-metastatic Activities

Cited by 30 publications

References 56 publications

Nanostructured materials for photodynamic therapy: synthesis, characterization and in vitro activity

Nanostructured materials for photodynamic therapy: synthesis, characterization and in vitro activity

Permanent Photodynamic Activation of the Cholecystokinin 2 Receptor

MPPa-PDT suppresses breast tumor migration/invasion by inhibiting AKT-NF-κB-dependent MMP-9 expression via ROS

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