aluminum-tetrasulfophthalocyanine and temoporfin

The aim of the present study was to systematically review the efficacy of photodynamic therapy (PDT) in the management of oral potentially-malignant disorders (PMDS) and head and neck squamous cell carcinoma (HNSCC).. From 1985 to 2015, PubMed/Medline, Google Scholar, EMBASE, and ISI Web of Knowledge were searched using different combinations of the following key words: PDT, oral precancer, leukoplakia, erythroplakia, erythroleukoplakia, verrucous hyperplasia, oral submucous fibrosis, and HNSCC. Review articles, experimental studies, case reports, commentaries, letters to the editor, unpublished articles, and articles published in languages other than English were excluded.. Twenty-six studies were included in the present study. The number of patients ranged from 2 to 147, with a mean age of 50-67 years. The reported numbers of PMDS and HNSCC ranged between 5 and 225. Photosensitizers used were aminolevulinic acid, meta-tetrahydroxyphenylchlorin, Foscan, hematoporphyrin derivatives, Photofrin, Photosan, and chlorine-e6. Laser wavelength, power density, irradiation duration were 585-652 nm, 50-500 mW/cm. PDT is effective in the management of PMDS and HNSCC.

Topics: Aminolevulinic Acid; Carcinoma, Squamous Cell; Chlorophyllides; Databases, Factual; Dihematoporphyrin Ether; Erythroplasia; Head and Neck Neoplasms; Hematoporphyrins; Humans; Hyperplasia; Indoles; Laser Therapy; Lasers; Leukoplakia; Leukoplakia, Oral; Mesoporphyrins; Oral Submucous Fibrosis; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Porphyrins; Squamous Cell Carcinoma of Head and Neck; Treatment Outcome

Photodynamic therapy is an attractive technique for various skin tumors and non-cancerous skin lesions. However, while the aim of photodynamic therapy is to target and damage only the malignant cells, it unavoidably affects some of the healthy cells surrounding the tumor as well. However, data on the effects of PDT to normal cells are scarce, and the characterization of the pathways activated after the photodamage of normal cells may help to improve clinical photodynamic therapy. In our study, primary human epidermal keratinocytes were used to evaluate photodynamic treatment effects of photosensitizers with different subcellular localization. We compared the response of keratinocytes to lysosomal photodamage induced by phthalocyanines, aluminum phthalocyanine disulfonate (AlPcS

Topics: Apoptosis; Autophagy; Cell Differentiation; Computer Simulation; Humans; Indoles; Isoindoles; Keratinocytes; Kinetics; Lysosomes; Mesoporphyrins; Models, Biological; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents

In vitro experiments in plastic receptacles are the basis of characterization of new photosensitizers (PSs) for the photodynamic therapy. We recently reported that lipophilic PSs adhere to cell culture microplates in a kinetic-like manner (Engelhardt et al., 2011). In the current study, we examined the interaction and phototoxic effects of the microplate-adhered PS in cancer cells. Therefore, we preloaded microplates with hypericin, Foscan, PVP-hypericin, or aluminum (III) phthalocyanine tetrasulfonate chloride (AlPCS4) for 24 hours and measured the PS distribution after addition of A431 human carcinoma cells: following another 24 hours up to 68% of hypericin were detected in the cell fraction. The hydrophilic PVP-hypericin and AlPCS4 also diffused into the cells, but the quantities of PS adherence were considerably lower. Microplate-adhered Foscan appeared not to be redistributed. In contrast to the hydrophilic PSs, the cellular phototoxicity of microplate-adhered lipophilic PS was high, independent of whether the PS (i) was pre-loaded onto microplates or (ii) added simultaneously with the cells or (iii) one day after cell seeding. Based on these results, we suggest testing lipophilic PS dyes for their adherence to microplates. Furthermore, the ability of plastic materials to (reversibly) store PSs might represent a new approach for the PS delivery or the development of antimicrobial coatings.

Topics: Anthracenes; Carcinoma; Cell Adhesion; Cell Culture Techniques; Cell Line, Tumor; Cell Membrane; Culture Media; Dermatitis, Phototoxic; Drug Delivery Systems; Humans; Indoles; Mesoporphyrins; Organometallic Compounds; Perylene; Photochemotherapy; Photosensitizing Agents; Plastics

At present a wide range of photosensitizers are employed in photodynamic therapy (PDT) that have very different characteristics. Although, countless in vitro studies on the attributes of photosensitizers do exist, a direct comparison of these substances on one cell line are rare and may contribute to the choice of the optimal photoactive substance for a specific application. We therefore evaluated the properties of six widespread photosensitizers, namely Foscan, Fospeg, hypericin, aluminum (III) phthalocyanine tetrasulfonate chloride (AlPcS(4)), 5-aminolevulinic acid (ALA), and Photofrin in terms of: (i) cytotoxicity without illumination, (ii) phototoxicity, (iii) cellular uptake and release, and (iv) apoptosis induction in A431 human epidermoid carcinoma cells using comparable illumination regimens. We clearly show that meso-tetrahydroxyphenylchlorin (mTHPC, Foscan) is a very effective photosensitizer inducing high phototoxicity at very low concentrations. Similar in vitro characteristics and phototoxicity were observed for Fospeg, the water-soluble formulation of mTHPC. Hypericin, a photosensitizer extracted from plants of the Hypericum genus, is very effective in inducing apoptosis over a wide range of light fluences. AlPcS(4) absorbs light of 674 nm wavelength providing a higher penetration depth in tissue. Its hydrophilic character allows for application as aqueous solution. ALA can be administered at very high concentrations without producing cytotoxic effects in the dark. The intracellular concentration of protoporphyrin IX rapidly decreases after withdrawal of ALA, thus minimizing the period of light sensitivity post PDT. Among all photosensitizers Photofrin has most clinical approvals and serves as standard.

Topics: Aminolevulinic Acid; Anthracenes; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Dihematoporphyrin Ether; Humans; Indoles; Mesoporphyrins; Organometallic Compounds; Perylene; Photochemotherapy; Photosensitizing Agents

A challenge in photodynamic therapy (PDT) is to improve the tumour selectivity of the photosensitizers by using monoclonal antibodies (MAbs). With this aim, we developed MAb-conjugates with the hydrophobic photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) and with the hydrophilic sensitizer aluminium (III) phthalocyanine tetrasulfonate (AlPcS(4)). The capacity of these photoimmunoconjugates for selective targeting of squamous cell carcinoma (SCC) in vivo was demonstrated previously in SCC-bearing nude mice. Preliminary in vitro PDT studies with the vulvar SCC cell line A431 showed promising phototoxicity with both sensitizers when coupled to the internalizing MAb 425. To rank the photosensitizers for their potential in photoimmunotherapy, we herein describe an extensive in vitro evaluation of mTHPC-MAb and AlPcS(4)-MAb conjugates. Both classes of conjugates were directly compared using 5 different SCC cell lines as target and 3 different MAbs (BIWA 4, E48 and 425) for tumour cell targeting. In contrast to free AlPcS(4) (IC(50) > or = 700 nM), MAb-conjugated AlPcS(4) was found to be highly phototoxic in PDT in all 5 cell lines. AlPcS(4)-BIWA 4 was most consistently effective with IC(50) values ranging from 0.06-5.4 nM. mTHPC-MAb conjugates were in general hardly effective. Phototoxicity (log IC(50)) of the AlPcS(4)-MAb conjugates was found to be strongly correlated with their total cell binding capacity (internalized and surface bound) and to be less correlated with their internalization capacity. In conclusion, these data show a high potential of AlPcS(4)-MAb conjugates in comparison to mTHPC-MAb conjugates for use in PDT.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cell Division; Head and Neck Neoplasms; Humans; Immunoconjugates; Indoles; Mesoporphyrins; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Tumor Cells, Cultured