Charged groups on pyropheophorbide-based photosensitizers dictate uptake by tumor cells and photodynamic therapy efficacy

2021 ◽  
pp. 112375
Author(s):  
Courtney Saenz ◽  
Manivannan Ethirajan ◽  
Erin C. Tracy ◽  
Mary-Jo Bowman ◽  
Joseph Cacaccio ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Therapy Efficacy

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.

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

Current phthalocyanines delivery systems in photodynamic therapy: an updated review

2021 ◽  
Vol 28 ◽  
Author(s):  
Mariana Miretti ◽  
Cesar German Prucca ◽  
Tomas Cristian Tempesti ◽  
Maria Teresa Baumgartner
Keyword(s):  
Photodynamic Therapy ◽  
Polymeric Micelles ◽  
Polymeric Nanoparticles ◽  
Aqueous Media ◽  
Delivery Systems ◽  
Current Status ◽  
Oxygen Species ◽  
Cancer Treatments ◽  
Therapy Efficacy ◽  
Cellular Components

: Photodynamic therapy has emerged as an effective therapeutic alternative to treat oncological, cardiovascular, dermatological, infectious, and ophthalmic diseases. Photodynamic therapy combines the action of a photosensitizer with light in the presence of oxygen to generate reactive oxygen species capable of reacting with cellular components resulting in injury and, consequently, inducing cellular death. Phthalocyanines are considered good photosensitizers, although most of them are lipophilic, difficulting their administration for clinical use. A strategy to overcome the lack of solubility of phthalocyanines in aqueous media is to incorporate them into different delivery systems. The present review aimed to summarize the current status of the main drug delivery systems used for Zn and Al phthalocyanines and their effect in photodynamic therapy, reported in the last five years. Liposomes, polymeric micelles, polymeric nanoparticles, and gold-nanoparticles constituted some of the most used carriers and were discussed in this review. The latest studies reported strongly suggests that the application of nanotechnologies as delivery systems allow an increase in photodynamic therapy efficacy and reduce side-effects associated with the phthalocyanine administration, which represents a promise for cancer treatments.

scholarly journals Why TKI Therapy Targeting Minority Population of Tumor Cells Could Achieve Complete Control of Entire Tumor: The Self-Driven and Non-Autonomous Replication in Cancer and Their Connection through Inflammation

2020 ◽  
Vol 5 (3) ◽  
Keyword(s):  
Tumor Cells ◽  
Kinase Inhibitors ◽  
Extended Period ◽  
Target Population ◽  
Minority Population ◽  
Complete Control ◽  
Therapy Efficacy ◽  
The Common ◽  
Two Populations ◽  
Cancer Clinic

Despite wide application of targeted therapy with small molecule tyrosine kinase inhibitors (TKI) in cancer clinic, some questions for the mechanisms of these inhibitors remain unresolved. For example, how can a tumor be completely controlled for extended period (more than a year) by the drug when the target population in the tumor is not even in majority? Here we report our observations in one such case of lung cancer and provide explanation for this long-awaited clinical puzzle. Our analyses indicate that in many of the similar cases, the cancer is composed of two populations of tumor cells, one capable of autonomous (or self-driven) replication through the known mutation, and the replication of the other is inflammationdependent. The connection is through inflammation induced by the tumor cells capable of self-driven replication. The control of this population by TKI terminates induction of inflammation thus results in control of the non-autonomous population. The identification of these two replicating tumor cells and their relationship holds many answers to current clinical confusions in many cancer cases where accelerated tumor progression, high inflammation and loss of therapy efficacy are often the common feature. By understanding these processes, we can begin to manage cancer in a more proactive manner to avoid the once recognized unavoidable fate of cancer

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.

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.

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...

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