scholarly journals PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4477 ◽  
Author(s):  
Vladimíra Pavlíčková ◽  
Silvie Rimpelová ◽  
Michal Jurášek ◽  
Kamil Záruba ◽  
Jan Fähnrich ◽  
...  

Purpurin 18 derivatives with a polyethylene glycol (PEG) linker were synthesized as novel photosensitizers (PSs) with the goal of using them in photodynamic therapy (PDT) for cancer. These compounds, derived from a second-generation PS, exhibit absorption at long wavelengths; considerable singlet oxygen generation and, in contrast to purpurin 18, have higher hydrophilicity due to decreased logP. Together, these properties make them potentially ideal PSs. To verify this, we screened the developed compounds for cell uptake, intracellular localization, antitumor activity and induced cell death type. All of the tested compounds were taken up into cancer cells of various origin and localized in organelles known to be important PDT targets, specifically, mitochondria and the endoplasmic reticulum. The incorporation of a zinc ion and PEGylation significantly enhanced the photosensitizing efficacy, decreasing IC50 (half maximal inhibitory compound concentration) in HeLa cells by up to 170 times compared with the parental purpurin 18. At effective PDT concentrations, the predominant type of induced cell death was apoptosis. Overall, our results show that the PEGylated derivatives presented have significant potential as novel PSs with substantially augmented phototoxicity for application in the PDT of cervical, prostate, pancreatic and breast cancer.

RSC Advances ◽  
2015 ◽  
Vol 5 (100) ◽  
pp. 81897-81904 ◽  
Author(s):  
Junliang Lv ◽  
Xin Zhang ◽  
Nana Li ◽  
Baoju Wang ◽  
Sailing He

Gold bipyramid-mediated singlet oxygen generation for photodynamic therapy of cancer cells in the optical biological window.


2017 ◽  
Vol 5 (35) ◽  
pp. 7319-7327 ◽  
Author(s):  
Minchang Lee ◽  
Hansang Lee ◽  
N. Vijayakameswara Rao ◽  
Hwa Seung Han ◽  
Sangmin Jeon ◽  
...  

Photodynamic therapy (PDT) has been extensively investigated to treat cancer since it induces cell death through the activation of photosensitizers by light.


Cancers ◽  
2011 ◽  
Vol 3 (2) ◽  
pp. 2516-2539 ◽  
Author(s):  
Pawel Mroz ◽  
Anastasia Yaroslavsky ◽  
Gitika B Kharkwal ◽  
Michael R. Hamblin

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1773
Author(s):  
Gauta Gold Matlou ◽  
Heidi Abrahamse

Hybrid inorganic-organic core-shell nanoparticles (CSNPs) are an emerging paradigm of nanodrug carriers in the targeted photodynamic therapy (TPDT) of cancer. Typically, metallic cores and organic polymer shells are used due to their submicron sizes and high surface to volume ratio of the metallic nanoparticles (NPs), combined with enhances solubility, stability, and absorption sites of the organic polymer shell. As such, the high loading capacity of therapeutic agents such as cancer specific ligands and photosensitizer (PS) agents is achieved with desired colloidal stability, drug circulation, and subcellular localization of the PS agents at the cancer site. This review highlights the synthesis methods, characterization techniques, and applications of hybrid inorganic-organic CSNPs as loading platforms of therapeutic agents for use in TPDT. In addition, cell death pathways and the mechanisms of action that hybrid inorganic-organic core-shell nanodrug systems follow in TPDT are also reviewed. Nanodrug systems with cancer specific properties are able to localize within the solid tumor through the enhanced permeability effect (EPR) and bind with affinity to receptors on the cancer cell surfaces, thus improving the efficacy of short-lived cytotoxic singlet oxygen. This ability by nanodrug systems together with their mechanism of action during cell death forms the core basis of this review and will be discussed with an overview of successful strategies that have been reported in the literature.


2019 ◽  
Vol 70 (4) ◽  
pp. 1288-1292
Author(s):  
Natalia Radulea ◽  
Rica Boscencu ◽  
Radu Socoteanu ◽  
Gina Manda ◽  
Ionela Victoria Neagoe

This study include in the same frame promising structures tailored as photoactive agents for photodynamic therapy of cancer versus one of the most versatile cell lines from experimental point of view, fibroblasts type, subcutaneous connective tissues- L929. Transmembrane potential was studied establishing important features in the behavior of chemical vectors against cultured cells via membranar media. Two amphiphilic porphyrins, 5,15-bis-(4-hydroxy-3-methoxyphenyl)-10,20-bis-(4-carboxymethylphenyl)porphyrin and Zn(II)-5,15-bis-(4-hydroxy-3-methoxyphenyl)-10,20-bis-(4-carboxymethylphenyl)porphyrin were assessed in terms of the effect on membrane potential. The comparative effect of free base porphyrin and metalloporphyrin with amphiphilic structure, reveal hyperpolarization phenomena and bring informations about consequences of active compound concentration against cell membrane.


2018 ◽  
Vol 47 (16) ◽  
pp. 5582-5588 ◽  
Author(s):  
Yun Ma ◽  
Shujun Zhang ◽  
Huanjie Wei ◽  
Yafang Dong ◽  
Liang Shen ◽  
...  

A novel soft salt based photosensitizer was successfully developed for application in photodynamic therapy of cancer cells for the first time.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Mi Hyeon Cho ◽  
Yan Li ◽  
Pui-Chi Lo ◽  
Hyeri Lee ◽  
Yongdoo Choi

Abstract In this study, a fucoidan-based theranostic nanogel (CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve activatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy (PDT) to induce the complete death of cancer cells. A CFN-gel has nanomolar affinity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention effect. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation-induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. Since a CFN-gel also shows nanomolar affinity for the vascular endothelial growth factor, it also provides a significant anti-tumor effect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high efficacy and specificity.


2008 ◽  
Vol 20 (01) ◽  
pp. 9-17 ◽  
Author(s):  
Cheng-Liang Peng ◽  
Ping-Shan Lai ◽  
Ming-Jium Shieh

The asymmetric porphyrins with different substituents show various bioactivities in biomedical application. In this study, a series of asymmetric porphyrins with varying proportion of substituents, such as hydroxyphenyl and aminophenyl, were synthesized and characterized to evaluate their cell uptake, intracellular localization, cytotoxicities and phototoxicities in vitro. Among these synthesized porphyrins, 5-(4-aminophenyl)-10,15,20-tri-(4-hydroxyphenyl)-21,23H-porphyrin (porphyrin 5), which was mainly localized in mitochondria and with high quantum yields of singlet oxygen, is a potential candidate for photodynamic therapy. The effective phototoxicity of porphyrin 5 is mainly due to the higher extent in the cells and the selective mitochondria-localization. Comparing the partition coefficients of porphyrin derivatives, the best cellular uptake performs apparently with a partition coefficient (log p) ranging from about 1.7 to 1.9. In summary, higher quantum yields of singlet oxygen, and more specific mitochondrial localization of porphyrin 5 demonstrate its potential application in photodynamic therapy.


2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Elisa Panzarini ◽  
Valentina Inguscio ◽  
Luciana Dini

Photodynamic Therapy (PDT) is a non-invasive treatment for different pathologies, cancer included, using three key components: non-toxic light-activated drug (Photosensitizer, PS), visible light, and oxygen. Their interaction triggers photochemical reactions leading to Reactive Oxygen Species (ROS) generation, that mediate cytotoxicity and cell death. In the present paper, the most important findings about the synthetic dye Rose Bengal Acetate (RBAc), an emerging photosensitizer for its efficient induction of cell death, will be reported with the aim to integrate RBAc phototoxicity to novel therapeutic PDT strategies against tumour cells. After its perinuclear intracellular localization, RBAc causes multiple subcellular organelles damage, that is, mitochondria, Endoplasmic Reticulum (ER), lysosomes, and Golgi complex. Indeed, RBAc exerts long-term phototoxicity through activation of both caspase-independent and- dependent apoptotic pathways and autophagic cell death. In particular, this latter cell death type may promote cell demise when apoptotic machinery is defective. The deep knowledge of RBAc photocytotoxicity will allow to better understand its potential photomedicine application in cancer.


2015 ◽  
Vol 14 (8) ◽  
pp. 1390-1396 ◽  
Author(s):  
Pilar Acedo ◽  
Joanna Zawacka-Pankau

p53 is a powerful tumor suppressor and a critical sensor of cellular stress. This Perspective summarizes the role of p53 in response of cancer cells to photodynamic therapy – a field not fully explored yet.


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