Photodynamic therapy of cancer with liposomal photosensitizers

The photodynamic reaction involves the light-induced generation of an excited state in a photosensitizer molecule (PS), which then results in the formation of reactive oxygen species in the presence of oxygen, or a direct modification of a cellular molecule. Most PSs are porphyrinoids, which are highly lipophilic, and are administered usually in liposomes to facilitate their effective delivery to target cells. The currently available liposomal formulations are Visudyne® and Fospeg®. Novel PSs were developed and tested for their photodynamic activity against cancer cells. Several compounds were highly phototoxic to oral cancer cells both in free and liposome-encapsulated form, with nanomolar IC50 values. The lowest IC50s (7-13 nM) were obtained with a PS encapsulated in cationic liposomes

Current status of liposomal porphyrinoid photosensitizers

The complete eradication of various targets, such as infectious agents or cancer cells, while leaving healthy host cells untouched, is still a great challenge faced in the field of medicine. Photodynamic therapy (PDT) seems to be a promising approach for anticancer treatment, as well as to combat various dermatologic and ophthalmic diseases and microbial infections. The application of liposomes as delivery systems for porphyrinoids has helped overcome many drawbacks of conventional photosensitizers and facilitated the development of novel effective photosensitizers that can be encapsulated in liposomes. The development, preclinical studies and future directions for liposomal delivery of conventional and novel photosensitizers are reviewed. © 2013 Elsevier Ltd. All rights reserved

Physicochemical properties of liposome-incorporated 2-(morpholin-4-yl)ethoxy phthalocyanines and their photodynamic activity against oral cancer cells

Three 2-(morpholin-4-yl)ethoxy-substituted phthalocyanines with zinc(II) or magnesium(II) ion in the core were subjected to optical and photochemical studies, and their photodynamic activity against oral cancer cell lines was evaluated. Phthalocyanine derivatives were studied both as free compounds and after incorporation into liposomes used as drug delivery vehicles. The introduction of electron-donating 2-(morpholin-4-yl)ethoxy groups in non-peripheral positions significantly affected physicochemical and optical properties of the phthalocyanines. The increased number of substituents led to increased hydrophilicity, decreased tendency to aggregate, and a larger shift of the phthalocyanine Q band toward the red region of the spectra. The incorporation of the hydrophobic zinc(II) phthalocyanine derivative possessing two 2-(morpholin-4-yl)ethoxy substituents into liposomes triggered most pronounced changes in its physicochemical properties compared to octasubstituted compounds. The disubstituted derivative expressed a promising biological effect against oral squamous cell carcinoma with IC50 values of 22 nM and 29 nM for the free and encapsulated compound, respectively. Our results indicate that liposomes can be used as a drug delivery vehicle for hydrophobic phthalocyanines in further biological studies

Physicochemical properties of liposome-incorporated 2-(morpholin-4-yl)ethoxy phthalocyanines and their photodynamic activity against oral cancer cells

The aim of the study was to develop a liposomal carrier for novel 2-(morpholin-4-yl)ethoxy-substituted phthalocyanines (Pcs 3 – 5) and to determine at what extent liposomal incorporation of Pcs 3 - 5 can affect physicochemical properties of these compounds and in vitro antiproliferative activity against oral cancer cells

Physicochemical properties of liposome-incorporated 2-(morpholin-4-yl)ethoxy phthalocyanines and their photodynamic activity against oral cancer cells

The aim of the study was to develop a liposomal carrier for novel 2-(morpholin-4-yl)ethoxy-substituted phthalocyanines (Pcs 3 – 5) and to determine at what extent liposomal incorporation of Pcs 3 - 5 can affect physicochemical properties of these compounds and in vitro antiproliferative activity against oral cancer cells

Antimicrobial and anticancer photodynamic activity of a phthalocyanine photosensitizer with N-methyl morpholiniumethoxy substituents in non-peripheral positions

Photodynamic therapy involves the use of a photosensitizer that is irradiated with visible light in the presence of oxygen, resulting in the formation of reactive oxygen species. A novel phthalocyanine derivative, the quaternary iodide salt of magnesium(II) phthalocyanine with N-methyl morpholiniumethoxy substituents, was synthesized, and characterized. The techniques used included mass spectrometry (MALDI TOF), UV–vis, NMR spectroscopy, and photocytotoxicity against bacteria, fungi and cancer cells. The phthalocyanine derivative possessed typical characteristics of compounds of the phthalocyanine family but the effect of quaternization was observed on the optical properties, especially in terms of absorption efficiency. The results of the photodynamic antimicrobial effect study demonstrated that cationic phthalocyanine possesses excellent photodynamic activity against planktonic cells of both Gram-positive and Gram-negative bacteria. The bactericidal effect was dose-dependent and all bacterial strains tested were killed to a significant degree by irradiated phthalocyanine at a concentration of 1 × 10− 4 M. There were no significant differences in the susceptibility of Gram-positive and Gram-negative bacteria to the applied photosensitizer. The photosensitivity of bacteria in the biofilm was lower than that in planktonic form. No correlation was found between the degree of biofilm formation and susceptibility to antimicrobial photodynamic inactivation. The anticancer activity of the novel phthalocyanine derivative was tested using A549 adenocarcinomic alveolar basal epithelial cells and the human oral squamous cell carcinoma cells derived from tongue (HSC3) or buccal mucosa (H413). No significant decrease in cell viability was observed under different conditions or with different formulations of the compound

Phthalocyanines functionalized with 2-methyl-5-nitro-1H-imidazolylethoxy and 1,4,7-trioxanonyl moieties and the effect of metronidazole substitution on photocytotoxicity

Four novel magnesium(II) and zinc(II) phthalocyanines bearing 1,4,7-trioxanonyl, polyether and/or (2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy, heterocyclic substituents at their non-peripheral positions were synthesized and assessed in terms of physicochemical and biological properties. Magnesium phthalocyanine derivatives bearing polyether substituents (Pc-1), a mixed system of polyether and heterocyclic substituents (Pc-3), and four heterocyclic substituents (Pc-4), respectively, were synthesized following the Linstead macrocyclization reaction procedure. Zinc phthalocyanine (Pc-2) bearing polyether substituents at non-peripheral positions was synthesized following the procedure in n-pentanol with the zinc acetate, and DBU. Novel phthalocyanines were purified by flash column chromatography and characterized using NMR, MS, UV-Vis and HPLC. Moreover, two precursors in macrocyclization reaction phthalonitriles were characterized using X-ray. Photophysical properties of the novel macrocycles were evaluated, including UV-Vis spectra analysis and aggregation study. All macrocycles subjected to singlet oxygen generation and the oxidation rate constant measurements exhibited lower quantum yields of singlet oxygen generation in DMSO than in DMF. In addition, the Pc-2 molecule was found to be the most efficient singlet oxygen generator from the group of macrocycles studied. The photocytotoxicity evaluated on the human oral squamous cell carcinoma cell line, HSC-3, for Pc-3 was significantly higher than that for Pc-1, Pc-2, and Pc-4. Interestingly, Pc-3 was found to be the most active macrocycle in vitro although its ability to generate singlet oxygen was significantly lower than those of Pc-1 and Pc-2. However, attempts to encapsulate phthalocyanines Pc-1-Pc-3 in liposomal membranes were unsuccessful. The phthalocyanine-nitroimidazole conjugate, Pc-4 was encapsulated in phosphatidylglycerol:phosphatidylcholine unilamellar liposomes and subjected to photocytotoxicity study. © 2013 Elsevier Inc