Chiral Alkyl Groups at Position 3(1′) of Pyropheophorbide-a Specify Uptake and Retention by Tumor Cells and Are Essential for Effective Photodynamic Therapy

2021 ◽  
Vol 64 (8) ◽  
pp. 4787-4809
Author(s):  
Ravindra R. Cheruku ◽  
Erin C. Tracy ◽  
Walter Tabaczynski ◽  
Joseph R. Missert ◽  
Heinz Baumann ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Alkyl Groups ◽  
Pyropheophorbide A

Toward targeted photodynamic therapy

2011 ◽  
Vol 83 (4) ◽  
pp. 733-748 ◽  
Author(s):  
David Phillips
Keyword(s):  
Monoclonal Antibody ◽  
Photodynamic Therapy ◽  
Mouse Model ◽  
Tumor Cells ◽  
Water Solubility ◽  
Human Tumor ◽  
Antibody Fragments ◽  
Cell Kill ◽  
Pyropheophorbide A ◽  
Porphyrin Dimer

The sensitizers in common use for photodynamic therapy (PDT) are summarized, and approaches to the improvement of these outlined. Selectivity in the targeting of sensitizers to tumor cells and tissue is highly desirable, as is water solubility and prevention of aggregation. Some new free sensitizers are described, based upon the pyropheophorbide a (PPa) structure, and their photophysical properties, distribution in cells via confocal fluorescence microscopy, and cell kill properties described. A novel approach to targeting is to covalently attach such sensitizers to monoclonal antibody fragments, and recent work on the attachment of pyropheophorbide a to such monoclonal antibody fragments is reviewed, with a demonstration of the increased efficiency of cell kill, and the treatment of a solid human tumor in a mouse model described. Finally, an alternative method of achieving selectivity based upon two-photon excitation (TPE) using porphyrin dimer sensitizers is reviewed, and the use of these to kill tumor cells is compared with the use of a commercially available PDT sensitizer (Visudyne). TPE of a porphyrin dimer sensitizer is shown to be capable of sealing blood vessels in a mouse model.

Optical Properties of Photodynamic Therapy Drugs in Different Environments: The Paradigmatic Case of Temoporfin

2020 ◽  
Author(s):  
busenur Aslanoglu ◽  
Ilya Yakavets ◽  
Vladimir Zorin ◽  
Henri-Pierre Lassalle ◽  
Francesca Ingrosso ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Optical Properties ◽  
Photodynamic Therapy ◽  
Minimally Invasive ◽  
Visible Light ◽  
Cancer Treatment ◽  
Singlet Oxygen ◽  
Tumor Cells ◽  
Molecular Oxygen ◽  
Computational Tools

Computational tools have been used to study the photophysical and photochemical features of photosensitizers in photodynamic therapy (PDT) –a minimally invasive, less aggressive alternative for cancer treatment. PDT is mainly based by the activation of molecular oxygen through the action of a photoexcited sensitizer (photosensitizer). Temoporfin, widely known as mTHPC, is a second-generation photosensitizer, which produces the cytotoxic singlet oxygen when irradiated with visible light and hence destroys tumor cells. However, the bioavailability of the mostly hydrophobic photosensitizer, and hence its incorporation into the cells, is fundamental to achieve the desired effect on malignant tissues by PDT. In this study, we focus on the optical properties of the temoporfin chromophore in different environments –in <i>vacuo</i>, in solution, encapsulated in drug delivery agents, namely cyclodextrin, and interacting with a lipid bilayer.

scholarly journals BSA-encapsulated cyclometalated iridium complexes as nano-photosensitizers for photodynamic therapy of tumor cells

RSC Advances ◽  
2021 ◽  
Vol 11 (25) ◽  
pp. 15323-15331
Author(s):  
Yao Xu ◽  
Xiang Wang ◽  
Kang Song ◽  
Jun Du ◽  
Jinliang Liu ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Singlet Oxygen ◽  
Tumor Cells ◽  
Iridium Complexes

Three new iridium complexes were synthesized and fabricated with BSA to form nano-photosensitizers, which can catalyze oxygen to produce singlet oxygen to achieve photodynamic therapy of tumor cells.

Structural and Epimeric Isomers of HPPH [3-Devinyl 3-{1-(1-hexyloxy) ethyl}pyropheophorbide-a]: Effects on Uptake and Photodynamic Therapy of Cancer

2017 ◽  
Vol 12 (4) ◽  
pp. 933-946 ◽  
Author(s):  
Courtney Saenz ◽  
Ravindra R. Cheruku ◽  
Tymish Y. Ohulchanskyy ◽  
Penny Joshi ◽  
Walter A. Tabaczynski ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Photodynamic Therapy Of Cancer ◽  
Pyropheophorbide A

scholarly journals Photosensitizer Chlorin e6 Internalization into Tumor Cells in Phospholipid Nanoparticles Conjugated with Peptide Containing the NGR Sequence

2018 ◽  
Vol 1 (4) ◽  
pp. e00063 ◽  
Author(s):  
V.N. Prozorovskiy ◽  
L.V. Kostryukova ◽  
E.I. Korotkevich ◽  
T.I. Torkhovskaya ◽  
G.E. Morozevich ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Amino Acid ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Aminopeptidase N ◽  
Chlorin E6 ◽  
Phospholipid Nanoparticles ◽  
Chlorine E6 ◽  
Targeting Peptide ◽  
Mcf 7

The possibility of increased internalization of the photosensitizer chlorin e6 in tumor cells was investigatedusing soy phosphatidylcholine nanoparticles 20-30 nm with or without attached peptide containing Asn-Gly-Arg (NGR) motif was studied. This amino acid sequence exhibits affinity to aminopeptidase N (CD13), wich is overexpressed in a number of tumor cells and vessels. Nanoparticles with chlorin e6 were prepared with added of distearoylphosphatidylcholine (DSPE) conjugated through PEG with a hexapeptide containing the NGR sequence, and then were incubated with tumor cells НерG2 and MCF-7. Chlorin e6 accumulation in СD13-negative cells (MCF-7) did not depend on the presence of peptide NGR in nanoparticles. However, for НерG2 cells a twofold increase of chlorine e6 internalization was observed as compared with the same particles without NGR. Differences in the response of these two cell lines, differed in expression of aminopeptidase N (APN), suggest the possibility of this protein using for targeted delivery. The prospectivity of usage of phospholipids nanoparticles conjugated with targeting peptide for photodynamic therapy is discussed, taking into account possible variation of APN expression, inherent for many solid tumors.

scholarly journals Phenalenone‐photodynamic therapy induces apoptosis on human tumor cells mediated by caspase‐8 and p38‐MAPK activation

2018 ◽  
Vol 57 (11) ◽  
pp. 1525-1539 ◽  
Author(s):  
María L. Salmerón ◽  
José Quintana‐Aguiar ◽  
Juan V. De La Rosa ◽  
Félix López‐Blanco ◽  
Antonio Castrillo ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
P38 Mapk ◽  
Human Tumor ◽  
Caspase 8 ◽  
Human Tumor Cells ◽  
Mapk Activation

Dual-responsive nanoplatform with feedback amplification improves antitumor efficacy of photodynamic therapy

Nanoscale ◽  
2022 ◽  
Author(s):  
Yuan Xue ◽  
Shuting Bai ◽  
Leilei Wang ◽  
Shi Luo ◽  
Zhirong Zhang ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Side Effects ◽  
Tumor Cells ◽  
Delivery System ◽  
Antitumor Efficacy ◽  
Tumor Uptake ◽  
Dual Responsive ◽  
Intracellular Release ◽  
Enhance Efficiency

A good photosensitizer (PS) delivery system could enhance efficiency and reduce side effects of anti-tumor photodynamic therapy (PDT) by improving accumulation in tumor, uptake by tumor cells, and intracellular release...

Prospective application of phthalocyanines in the photodynamic therapy against microorganisms and tumor cells: A mini-review

2020 ◽  
Vol 32 ◽  
pp. 102032
Author(s):  
Karen Loraine Macena Santos ◽  
Rafaella Moreno Barros ◽  
Diego Paulo da Silva Lima ◽  
Adenia Mirela Alves Nunes ◽  
Mariana Rillo Sato ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Prospective Application

scholarly journals Mitotic Catastrophe Induced in HeLa Tumor Cells by Photodynamic Therapy with Methyl-aminolevulinate

2019 ◽  
Vol 20 (5) ◽  
pp. 1229 ◽  
Author(s):  
Marta Mascaraque ◽  
Pablo Delgado-Wicke ◽  
Alejandra Damian ◽  
Silvia Lucena ◽  
Elisa Carrasco ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Protoporphyrin Ix ◽  
Aurora Kinase ◽  
Mitotic Catastrophe ◽  
Mitotic Apparatus ◽  
Human Carcinoma ◽  
Cancer Cell Death ◽  
Multipolar Spindles ◽  
Methyl Aminolevulinate

Photodynamic therapy (PDT) constitutes a cancer treatment modality based on the administration of a photosensitizer, which accumulates in tumor cells. The subsequent irradiation of the tumoral area triggers the formation of reactive oxygen species responsible for cancer cell death. One of the compounds approved in clinical practice is methyl-aminolevulinate (MAL), a protoporphyrin IX (PpIX) precursor intermediate of heme synthesis. We have identified the mitotic catastrophe (MC) process after MAL-PDT in HeLa human carcinoma cells. The fluorescence microscopy revealed that PpIX was located mainly at plasma membrane and lysosomes of HeLa cells, although some fluorescence was also detected at endoplasmic reticulum and Golgi apparatus. Cell blockage at metaphase-anaphase transition was observed 24 h after PDT by phase contrast microscopy and flow cytometry. Mitotic apparatus components evaluation by immunofluorescence and Western blot indicated: multipolar spindles and disorganized chromosomes in the equatorial plate accompanied with dispersion of centromeres and alterations in aurora kinase proteins. The mitotic blockage induced by MAL-PDT resembled that induced by two compounds used in chemotherapy, taxol and nocodazole, both targeting microtubules. The alterations in tumoral cells provided evidence of MC induced by MAL-PDT, resolving mainly by apoptosis, directly or through the formation of multinucleate cells.

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