Maltotriose-conjugation to a fluorinated chlorin derivative generating a PDT photosensitizer with improved water-solubility

2016 ◽  
Vol 14 (14) ◽  
pp. 3608-3613 ◽  
Author(s):  
Atsushi Narumi ◽  
Takahiro Tsuji ◽  
Kosuke Shinohara ◽  
Hiromi Yamazaki ◽  
Moriya Kikuchi ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Water Solubility ◽  
Third Generation ◽  
Chlorin Derivative

A chlorin derivative was encircled with four maltotriose (Mal3) molecules to produce an oligosaccharide-conjugate meeting the requirements of a third generation photodynamic therapy (PDT) photosensitizer.

scholarly journals Nanoparticle-Based Drug Delivery Systems for Photodynamic Therapy of Metastatic Melanoma: A Review

2021 ◽  
Vol 22 (22) ◽  
pp. 12549
Author(s):  
Nkune Williams Nkune ◽  
Heidi Abrahamse
Keyword(s):  
Photodynamic Therapy ◽  
Metastatic Melanoma ◽  
Water Solubility ◽  
Three Dimensional ◽  
New Developments ◽  
Non Invasive ◽  
Promising Strategy ◽  
Skin Malignancy ◽  
Therapeutic Outcomes ◽  
D Cell

Metastatic melanoma (MM) is a skin malignancy arising from melanocytes, the incidence of which has been rising in recent years. It poses therapeutic challenges due to its resistance to chemotherapeutic drugs and radiation therapy. Photodynamic therapy (PDT) is an alternative non-invasive modality that requires a photosensitizer (PS), specific wavelength of light, and molecular oxygen. Several studies using conventional PSs have highlighted the need for improved PSs for PDT applications to achieve desired therapeutic outcomes. The incorporation of nanoparticles (NPs) and targeting moieties in PDT have appeared as a promising strategy to circumvent various drawbacks associated with non-specific toxicity, poor water solubility, and low bioavailability of the PSs at targeted tissues. Currently, most studies investigating new developments rely on two-dimensional (2-D) monocultures, which fail to accurately mimic tissue complexity. Therefore, three-dimensional (3-D) cell cultures are ideal models to resemble tumor tissue in terms of architectural and functional properties. This review examines various PS drugs, as well as passive and active targeted PS nanoparticle-mediated platforms for PDT treatment of MM on 2-D and 3-D models. The overall findings of this review concluded that very few PDT studies have been conducted within 3-D models using active PS nanoparticle-mediated platforms, and so require further investigation.

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.

Effective Monofunctional Azaphthalocyanine Photosensitizers for Photodynamic Therapy

2009 ◽  
Vol 62 (5) ◽  
pp. 425 ◽  
Author(s):  
Petr Zimcik ◽  
Miroslav Miletin ◽  
Veronika Novakova ◽  
Kamil Kopecky ◽  
Marcela Nejedla ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Carboxy Group ◽  
Rational Design ◽  
Photophysical Properties ◽  
Active Part ◽  
Third Generation ◽  
Highly Active ◽  
Low Degree ◽  
Band Absorption ◽  
Group B

In this work we present a rational design of the active part of third generation photosensitizers for photodynamic therapy based on phthalocyanine and an azaphthalocyanine core. The preferred zinc complexes of the AAAB type that contain bulky tert-butylsulfanyl substituents (A) and one carboxy group (B) have been synthesized by statistical condensation and fully characterized. The tetramerization was performed using magnesium(ii) butoxide followed by demetalation and insertion of ZnII. Compound 1 synthesized from 4,5-bis(tert-butylsulfanyl)phthalonitrile (A) and 2,3-dicyanoquinoxaline-6-carboxylic acid (B) exerted very promising photophysical properties (Q-band absorption at 726 nm, ϵ = 140000 M–1 cm–1), which allowed strong absorption of light at long wavelengths where the penetration of the light through human tissues is deeper. The very high singlet oxygen quantum yield of 1 (ΦΔ = 0.80) assures efficient photosensitization. As a result of bulky peripheral substituents, compound 1 shows good solubility in organic solvents with a low degree of aggregation, which makes it potentially viable for non-complicated modification. One carboxy group in the final structure of 1 allows simple binding to possible carriers. This compound is suitable for binding to targeting moieties to form the highly active part of a third-generation photosensitizer.

Synthesis and in vitro photodynamic therapy of chlorin derivative 131-ortho-trifluoromethyl-phenylhydrazone modified pyropheophorbide-a

2017 ◽  
Vol 87 ◽  
pp. 263-273 ◽  
Author(s):  
Jianjun Cheng ◽  
Wenting Li ◽  
Guanghui Tan ◽  
Zhiqiang Wang ◽  
Shuying Li ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Pyropheophorbide A ◽  
Chlorin Derivative

Taurine-modified Ru(ii)-complex targets cancerous brain cells for photodynamic therapy

2017 ◽  
Vol 53 (44) ◽  
pp. 6033-6036 ◽  
Author(s):  
Enming Du ◽  
Xunwu Hu ◽  
Sona Roy ◽  
Peng Wang ◽  
Kieran Deasy ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Quantum Yield ◽  
Cancer Cells ◽  
Water Solubility ◽  
Brain Cells ◽  
Independent Manner ◽  
Ru Complex

Symmetrical taurine modification not only enhances the intracellular affinity of a polypyridyl Ru-complex to cancer cells, but also boosts the quantum yield in a pH-independent manner without sacrificing water solubility for cytosolic photosensitizers of photodynamic therapy, with prominent efficacy in cancerous brain cells.

scholarly journals Recent Progress in Metal-Based Nanoparticles Mediated Photodynamic Therapy

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1704 ◽  
Author(s):  
Jingyao Sun ◽  
Semen Kormakov ◽  
Ying Liu ◽  
Yao Huang ◽  
Daming Wu ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Recent Progress ◽  
Water Solubility ◽  
Research Progress ◽  
Visible Range ◽  
Light Penetration ◽  
Potential Toxicity ◽  
Future Directions ◽  
Administration Routes ◽  
Recent Research Progress

Photodynamic therapy (PDT) is able to non-invasively treat and diagnose various cancers and nonmalignant diseases by combining light, oxygen, and photosensitizers (PSs). However, the application of PDT is hindered by poor water solubility and limited light-penetration depth of the currently available photosensitizers (PSs). Water solubility of PSs is crucial for designing pharmaceutical formulation and administration routes. Wavelength of light source at visible range normally has therapeutic depth less than 1 mm. In this review, focus is on the recent research progress of metal-based nanoparticles being applied in PDT. The potential toxicity of these nanoscales and future directions are further discussed.

scholarly journals Use of Cyclodextrins in Anticancer Photodynamic Therapy Treatment

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1936 ◽  
Author(s):  
Amina Ben Mihoub ◽  
Ludivine Larue ◽  
Albert Moussaron ◽  
Zahraa Youssef ◽  
Ludovic Colombeau ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Photodynamic Therapy ◽  
Molecular Oxygen ◽  
Inclusion Complexes ◽  
Water Solubility ◽  
Cellular Damage ◽  
Hybrid Nanoparticles ◽  
Binding Modes

Photodynamic therapy (PDT) is mainly used to destroy cancerous cells; it combines the action of three components: a photoactivatable molecule or photosensitizer (PS), the light of an appropriate wavelength, and naturally occurring molecular oxygen. After light excitation of the PS, the excited PS then reacts with molecular oxygen to produce reactive oxygen species (ROS), leading to cellular damage. One of the drawbacks of PSs is their lack of solubility in water and body tissue fluids, thereby causing low bioavailability, drug-delivery efficiency, therapeutic efficacy, and ROS production. To improve the water-solubility and/or drug delivery of PSs, using cyclodextrins (CDs) is an interesting strategy. This review describes the in vitro or/and in vivo use of natural and derived CDs to improve antitumoral PDT efficiency in aqueous media. To achieve these goals, three types of binding modes of PSs with CDs are developed: non-covalent CD–PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies. This review is divided into three parts: (1) non-covalent CD-PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies, (2) incorporating CD–PS systems into hybrid nanoparticles (NPs) using up-converting or other types of NPs, and (3) CDs with fullerenes as PSs.

scholarly journals Smart Polymeric Delivery System for Antitumor and Antimicrobial Photodynamic Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhijia Wang ◽  
Fu-Jian Xu ◽  
Bingran Yu
Keyword(s):  
Photodynamic Therapy ◽  
Bacterial Infections ◽  
Water Solubility ◽  
Polymeric Materials ◽  
Delivery Systems ◽  
Antimicrobial Photodynamic Therapy ◽  
Oxygen Species ◽  
Infection Site ◽  
Polymeric Delivery ◽  
Similarities And Differences

Photodynamic therapy (PDT) has attracted tremendous attention in the antitumor and antimicrobial areas. To enhance the water solubility of photosensitizers and facilitate their accumulation in the tumor/infection site, polymeric materials are frequently explored as delivery systems, which are expected to show target and controllable activation of photosensitizers. This review introduces the smart polymeric delivery systems for the PDT of tumor and bacterial infections. In particular, strategies that are tumor/bacteria targeted or activatable by the tumor/bacteria microenvironment such as enzyme/pH/reactive oxygen species (ROS) are summarized. The similarities and differences of polymeric delivery systems in antitumor and antimicrobial PDT are compared. Finally, the potential challenges and perspectives of those polymeric delivery systems are discussed.

scholarly journals Chlorin e6-Biotin Conjugates for Tumor-Targeting Photodynamic Therapy

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7342
Author(s):  
Wei Liu ◽  
Xingqun Ma ◽  
Yingying Jin ◽  
Jie Zhang ◽  
Yang Li ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Hela Cells ◽  
Tumor Targeting ◽  
Laser Scanning ◽  
Water Solubility ◽  
Laser Scanning Microscopy ◽  
Chlorin E6 ◽  
Confocal Laser ◽  
Oxygen Generation ◽  
Targeting Ability

To improve the tumor-targeting efficacy of photodynamic therapy, biotin was conjugated with chlorin e6 to develop a new tumor-targeting photosensitizer, Ce6-biotin. The Ce6-biotin had good water solubility and low aggregation. The singlet-oxygen generation rate of Ce6-biotin was slightly increased compared to Ce6. Flow cytometry and confocal laser scanning microscopy results confirmed Ce6-biotin had higher binding affinity toward biotin-receptor-positive HeLa human cervical carcinoma cells than its precursor, Ce6. Due to the BR-targeting ability of Ce6-biotin, it exhibited stronger cytotoxicity to HeLa cells upon laser irradiation. The IC50 against HeLa cells of Ce6-biotin and Ce6 were 1.28 µM and 2.31 µM, respectively. Furthermore, both Ce6-biotin and Ce6 showed minimal dark toxicity. The selectively enhanced therapeutic efficacy and low dark toxicity suggest that Ce6-biotin is a promising PS for BR-positive-tumor-targeting photodynamic therapy.

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