phytochlorin 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 Review articles, experimental studies, case reports, commentaries, letters to the editor, unpublished articles, and articles published in languages other than English were excluded..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

Tailor-made drug solubilizers are studied based on peptide-poly(ethylene glycol) conjugates, which exhibit peptide segments constituting binding motifs for the small-molecule drugs of interest to render them water-soluble. Suitable 7mer peptides are selected via combinatorial means by screening large one-bead-one-compound (OBOC) peptide libraries. The capability of the screening method to read out structural detail of the drugs is investigated by comparing three related photosensitizers (Chlorin E6 (Ce6), Pheophorbide A (Pba) and meta-tetra(hydroxyphenyl)chlorin (m-THPC), which are applicable for photodynamic cancer therapy. The screening procedure delivers de novo solubilizers that show the best solubilization efficiency for the drug the screening is performed with. While molecular recognition events between peptide and drug are not expected to be found, significant binding capacity differences of, e.g., the Ce6-solubilizer for Pba are suggesting selectivity in drug binding, even among structurally closely related drugs. Cyro-Electron microscopy revealed the formation of colloidal aggregates between drug moieties and peptide conjugates. Insights into relevant amino acids in the identified peptide sequences are gained by studying capacities of systematic point mutations (alanine scans), enabling understanding of drug-binding motifs. These reveal the importance of sequence positioning of appropriate H-bonding between polar functional groups of the peptide and the drugs, which agrees well with computational binding studies performed on drug/peptide model complexes.

Topics: Amino Acid Sequence; Chlorophyll; Chlorophyllides; Mesoporphyrins; Models, Molecular; Peptides; Photochemotherapy; Photosensitizing Agents; Polyethylene Glycols; Porphyrins; Solubility

The porphyrin and chlorin parent compounds constitute the base of many potent photosensitizers aimed to be utilized in photodynamic therapy (PDT). However, the photosensitizers available on the market today are not ideal for use in PDT; many of them suffering from drawbacks such as long-lasting photosensitization or absorption at wavelengths below the optimal tissue penetration. This has emphasized the need of new photosensitizers with improved photodynamic properties. In the present study we have used density functional theory based methods to design new chlorin compounds with conjugated substituents such as vinyl groups and carboxylic acids, aiming for strong absorption in the therapeutic window of PDT. The specific substituent positions were found to have a significant effect on the spectra. A chlorin with four propenoic acids was able to red-shift the absorption the most compared with non-substituted chlorin, generating the red-most absorption at 755 nm, and with significantly enhanced oscillator strengths. The results from the present study constitute a useful starting point for further design of tetrapyrrole derivatives as improved photosensitizers.

Topics: Absorption; Chlorophyllides; Mesoporphyrins; Photosensitizing Agents; Porphyrins