In vivo and in vitro characterisation of a protoporphyrin IX-cyclic RGD peptide conjugate for use in photodynamic therapy.

Increasing treatment specificity is one of the major aims of cancer research. Photodynamic therapy is a clinically proven treatment for some cancers and certain other diseases. Photosensitisers generally have little intrinsic selectivity for tumours and any accumulation is dependent upon the type of tumour involved.

An overview of synthetic approaches to porphyrin, phthalocyanine, and phenothiazine photosensitizers for photodynamic therapy.

The mechanistic basis of photodynamic therapy is reviewed briefly, and the factors that are important in improving photosensitizers are examined. The methods for preparing the three main classes of PDT photosensitizers, namely, porphyrins, phthalocyanines, and phenothiazines, are reviewed.

The present and future role of photodynamic therapy in cancer treatment.

It is more than 25 years since photodynamic therapy (PDT) was proposed as a useful tool in oncology, but the approach is only now being used more widely in the clinic. The understanding of the biology of PDT has advanced, and efficient, convenient, and inexpensive systems of light delivery are now available. Results from well-controlled, randomised phase III trials are also becoming available, especially for treatment of non-melanoma skin cancer and Barrett's oesophagus, and improved photosensitising drugs are in development.

A comparative analysis of phenothiazinium salts for the photosensitisation of murine fibrosarcoma (RIF-1) cells in vitro.

Photodynamic therapy (PDT) is a treatment combining a photosensitiser, molecular oxygen and visible light of characteristic wavelength to produce cytotoxic reactive oxygen species (ROS). Within our centre, a series of phenothiazinium salts were synthesised and initial characterisation studies performed to determine any potential use for PDT. All photosensitisers within the series were shown to have useful spectral properties for PDT, with absorbance lambdamax above 667 nm.

Photosensitized inactivation of microorganisms.

Despite major advances in medicine in the last 100 years, microbiologically-based diseases continue to present enormous global health problems. New approaches that are effective, affordable and widely applicable and that are not susceptible to resistance are urgently needed. The photodynamic approach is known to meet at least some of these criteria and, with the creation and testing of new photosensitisers, may develop to meet all of them.

Chronic UVB exposure enhances in vitro percutaneous penetration of 5-aminulevulinic acid in hairless mouse skin.

Background And Objectives: (Pre)cancerous skin lesions accumulate more protoporphyrin IX (PpIX) upon topical application of 5-aminolevulinic acid (ALA) than the surrounding normal skin. This might be the result of a higher percutaneous penetration of ALA into (pre)cancerous skin.

Study Design/materials And Methods: ALA penetration through (1) healthy skin with intact stratum corneum, (2) healthy skin with reduced stratum corneum (i.

Effect of elevating the skin temperature during topical ALA application on in vitro ALA penetration through mouse skin and in vivo PpIX production in human skin.

An approach to induce increased protoporphyrin IX (PpIX) production in aminolevulinic acid (ALA)-based photodynamic therapy (PDT) of skin lesions is to elevate the skin temperature during topical ALA application. Increased skin temperature may increase the (depth of) penetration of ALA into the skin, which may in turn increase PpIX production (in deeper layers). The effect of skin temperature on in vitro ALA penetration into mouse skin was determined in an in vitro percutaneous penetration model at two different temperatures.

The solid-phase conjugation of purpurin-18 with a synthetic targeting peptide.

It has been demonstrated that efficient site-specific coupling of the highly active photodynamic therapy sensitiser purpurin-18 to the synthetic targeting peptide G-G-V-K-R-K-K-K-P-G-Y-G can be achieved with greater than 85% purity.

Fluorescence microspectroscopy technique for the study of intracellular protoporphyrin IX dynamics.

We describe a technique designed to monitor the fluorescence dynamics of photosensitizers used in photodynamic therapy (PDT) at micrometer-scale locations within individual formalin-fixed cells. The accumulation of protoporphyrin IX (PpIX) within keratinocytes and fibroblasts. following incubation with 5-aminolaevulinic acid (ALA), is shown to be dependent upon both incubation time and cell proliferation status.

Comparative in vitro percutaneous penetration of 5-aminolevulinic acid and two of its esters through excised hairless mouse skin.

Background And Objectives: ALA esters have been developed to improve PpIX production in ALA-PDT, but they do not perform as well in skin as they do in cells and the bladder.

Study Design/materials And Methods: The in vitro penetration across normal mouse skin of ALA and its methyl and hexyl ester was determined for different application concentrations. ALA and the esters were also applied to tape stripped skin to determine the effect of the stratum corneum.

A randomised, double-blind, placebo-controlled trial of photodynamic therapy using 5-aminolaevulinic acid for the treatment of cervical intraepithelial neoplasia.

Photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (ALA) has been used to treat histologically confirmed cervical intraepithelial neoplasia (CIN-I and -I/II) in a randomised, double-blind, placebo-controlled protocol. Fluorescence microscopy revealed that topical application of 3% ALA in Intrasite Gel to the cervix for 3 hr resulted in the accumulation of protoporphyrin IX in the cervical epithelium. Treatment of CIN with ALA-PDT was well tolerated, with only 3/12 patients in the PDT arm (0/13 in the placebo arm) reporting any discomfort during illumination.

In vitro photodynamic activity of a series of methylene blue analogues.

We have synthesized a series of symmetrical phenothiazines in which the methyl groups of methylene blue have been substituted by longer alkyl chains. Intrinsic photosensitizing ability was not altered by increasing the chain length. However, in vitro phototoxicity after 2 h incubation of RIF-1 murine fibrosarcoma cells followed the order n-propyl > n-pentyl > n-butyl > n-hexyl > ethyl > methyl, with ethyl and n-propyl analogues being 14- and 130-fold more phototoxic than methylene blue, respectively.

THE DEGRADATION OF CHLOROPHYLL - A BIOLOGICAL ENIGMA.

Some 10 tonnes of chlorophyll are destroyed each year on land and in the oceans. The fate of these chlorophylls is, however, largely unknown. This review describes the developmental stages at which chlorophyll breakdown occurs in aquatic and terrestrial biological systems, and the destruction arising from herbivory, disease, pollution and other physical hazards.