Search PubMed⌕ Search

Biomedical subjects

C Rimington

Publications and source records attributed to C Rimington.

At least 37 records · Page 2Linked to original sources
PubMed1988

Hematoporphyrin ethers--III. Cellular uptake and photosensitizing properties.

1. The cellular uptake and the efficiency in sensitizing cells to photoinactivation were determined for hematoporphyrin (Hp) diphenyl ether, Hp dicyclohexyl ether and Hp dihexyl ether. 2. The phenyl diether was taken up by the cells to the same degree as was the clinically used porphyrin preparation photofrin II, while the dihexyl and notably the dicyclohexyl ether were taken up 3-4 times better. 3. Furthermore, the quantum yields for photoinactivation of cells were similar for the three diethers and twice as large as that for photofrin II. 4. Fluorescence- and absorption spectroscopy indicate that these findings are related to the fact that photofrin II is much more aggregated in the cells than are the three Hp diethers. 5. When cells loaded with the porphyrins are incubated with porphyrin-free medium containing serum a certain percentage of the cell-bound drug is removed: 14% for photofrin II, 28% for Hp diphenyl ether, 50% for Hp dicyclohexyl ether and 20% for Hp dihexyl ether. 6. With respect to cell uptake and retention of the dyes, the data did not show any uniform relationship to the polarity of the drugs, in contrast to what has been found earlier for Hp diethers of linear hydrocarbons.

Chromatography, High Pressure Liquid↗
PubMed1987

Hematoporphyrin ethers--I. Generalized synthesis and chemical properties.

A series of hematoporphyrin di-ethers, from methyl to hexyl, has been prepared by a generalized procedure based on reaction of the selected carbinol with the HBr adduct of protoporphyrin, followed by hydrolysis of ester functions and chromatographic purification. Spectroscopic and other properties are reported. They crystallize well. HPLC retention time increases linearly with the number of carbon atoms in the alcohol employed. In previous work we have shown that the more hydrophobic ethers are very efficient photosensitizers of malignant cells.

Chemical Phenomena↗
PubMed1987

A comparison of different photosensitizing dyes with respect to uptake C3H-tumors and tissues of mice.

Nine dyes, all potential sensitizers for photodynamic cancer therapy (PDT), were injected in mice with C3H mammary carcinomas. Twenty-four hours later the animals were sacrificed and the dye concentrations in tumors and 9 other tissues were measured by means of spectrofluorimetry. The 9 dyes were: Photofrin II (PII), hematoporphyrin (HP)-di-hexyl-ether, PSD-007 (a sensitizer used in clinical trials in China), tetraphenyl porphine tetrasulfonate (TPPS4), tetra(3-hydroxy phenyl)porphyrin (3THPP), aluminium phthalocyanine tetrasulfonate (AlPCTS), aluminium phthalocyanine (AlPC), chlorin e6 (Chl e6) and merocyanine 540 (MC 540). The porphyrin precursor delta-aminolevulinic acid was also tested and found to induce porphyrin fluorescence in tumors and some other tissues. The best tumorlocalizer of those tested was 3THPP. This drug also showed a favorable tissue distribution. The following dyes showed lower skin/tumor concentration ratios than PII (the most widely used dye for PDT): Chl e6, PSD-007, HP-di-hexyl-ether and 3THPP. Low brain/tumor ratios were found for: PSD-007, HP-di-hexyl-ether, 3THPP, TPPS4 and AlPCTS.

Animals↗
PubMed1987

Cellular uptake and photosensitizing properties of hematoporphyrin di-ethers with similar chromatographic properties as the tumorlocalizing fraction of hematoporphyrin derivative.

The di-methyl-, di-ethyl-, di-propyl-, di-normal butyl-, and di-iso-butyl-ethers of hematoporphyrin were synthesized and shown to possess chromatographic properties similar to those of the tumorlocalizing components of hematoporphyrin derivative (Hpd). The cellular uptake of these ethers, as well as their retention in cells during incubation with porphyrin free medium, increased with decreasing polarity and so did their efficiency in sensitizing cultured cells to photoinactivation. The least polar of the porphyrin ethers tested showed up to a 10-fold stronger efficiency in sensitizing cultured cells to photoinactivation than Hpd and Photofrin II (P II).

Cell Line↗
PubMed1987

Porphyrin derivatives having physical and chemical characteristics similar to those of the active components of hematoporphyrin derivative and with very strong photosensitizing effects.

The tumour-localizing fraction of hematoporphyrin derivative (Hpd) is thought to possess an essentially diporphyrin ether structure or, alternatively, a diporphyrin ester structure, the properties of which facilitate its retention in malignant cells and its biological activity on irradiation. To elucidate this problem further, we have synthesized the dimethyl, diethyl, dipropyl, di-n-butyl and di-iso-butyl ethers of hematoporphyrin. These ethers show chromatographic properties very similar to those of the active components of Hpd. Furthermore, they are much better photosensitizers in a cellular system than are crude Hpd or Photofrin II, and, like the components of Hpd, they are taken up and retained by cells according to their degree of non-polarity.

Carcinoma in Situ↗
PubMed1987

Photodynamic therapy of C3H mouse mammary carcinoma with haematoporphyrin di-ethers as sensitizers.

Haematoporphyrin di-ethers were synthesized and tested as sensitizers for photodynamic therapy of C3H/Tif mammary tumours in mice. Growth curves of the tumours were determined by measuring the tumour volume. The animals were given 25 mg porphyrins kg-1 body weight i.p. and 24 h later exposed to 135 J cm-2 of 630 nm light at a fluence rate of 150 mW cm-2. The sensitizing efficiency of the ethers was measured in terms of the increase in growth time of the treated tumours, as compared with that of untreated controls, needed to reach a volume 5 times larger than that at the time of the treatment. This sensitizing efficiency increased with decreasing polarity, i.e. in the order di-methyl ether, di-propyl ether, dibutyl ether and di-amyl ether. Haematoporphyrin di-amyl ether was more efficient than haematoporphyrin derivative and insignificantly less efficient than photofrin II (DHE). This was true for sensitization of both tumours and normal tissue.

Animals↗
PubMed1985

The binding of dihematoporphyrin ether (photofrin II) to human serum albumin.

The variable aggregation of porphyrins such as Hp and Hpd introduces uncertainties and errors into attempts to measure their binding to proteins. Methods such as dialysis, ultrafiltration and gel chromatography, so frequently used, proved to be unreliable when applied to the binding of Hp to serum albumin. Quenching of tryptophan fluorescence will only occur at porphyrin binding sites which are closely situated to the tryptophan residue (1.7 nm). Porphyrin bound to more distant sites may not be included in this analytical procedure which must therefore be applied with reserve. In the present work, photofrin II (PII) was shown to consist of large aggregates greater than 20 000-30 000 Mr, solutions of which did not disaggregate on dilution down to 1 mumol/1. Addition of albumin resulted in a change in the absorption spectrum of PII. Thus, it was assumed that measurements of differential absorption gave the proportion of free-to-bound PII when serum albumin was added in graded amounts to its solution. By applying suitable calculations to the data, an association constant of 0.3 1/mumol +/- 30% was deducted. Hill plots of the binding data were linear with slopes close to unity. Experimentally determined uptake of PII by NHIK 3025 cells from solutions containing different amounts of HSA showed that the amount bound to the cells was proportional to the free PII. The kinetics of quenching of tryptophan fluorescence in HSA by PII indicates that there is one main porphyrin-binding site affecting this fluorescence. This binding site seems to have a slightly higher affinity for PII than the remaining sites. Up to 8 porphyrin rings of PII can be bound to an HSA molecule.

Cell Line↗
PubMed1984

Formation of metal complexes of tumor-localizing porphyrins.

Whereas the tumor localizer and photosensitizer hematoporphyrin derivative (Hpd) has its fluorescence emission maximum at 610-630 nm, several authors have reported that in aqueous solutions of hematoporphyrin (Hp) and Hpd, or in tumors after an injection of Hpd, a compound is formed which has its fluorescence emission maximum at 570-590 nm. This work (HPLC and fluorescence analysis) indicates that this peak is due to the formation of Zn-porphyrins either in vitro or in vivo. Cu- and Co-porphyrins may be formed as well, from traces of these metallic ions. In contrast to free porphyrins and Zn-porphyrins the latter complexes are non-fluorescent and do not act as photosensitizers.

Animals↗