<title>Photoproduct formation of endogeneous protoporphyrin and its photodynamic activity</title>
3
Citation
1
Reference
10
Related Paper
Abstract:
Human skin shows a strong autofluorescence in the red spectral region caused on the porphyrin production of the Gram positive lipophile skin bacterium Propionibacterium acnes. Irradiation of these bacteria reduces the integral fluorescence intensity and induces the formation of fluorescent photoproducts. The fluorescence band at around 670 nm and the decay times of around 1 ns and 5 ns are typical for protoporphyrin products. The photoproduct formation is connected with an increased absorption in the red spectral region. However the photodynamic activity of these photoproducts determined by scattering measurements on human erythrocytes is lower than that of protoporphyrin IX. 1:Keywords:
Protoporphyrin IX
Propionibacterium Acnes
Autofluorescence
Human skin
Cite
We report on the design and synthesis of a new type of 4-aminoquinoline-based molecular tweezer 1 which forms a stable host-guest complex with protoporphyrin IX (PPIX) via multiple interactions in a DMSO and HEPES buffer (pH 7.4) mixed solvent system. The binding constant for the 1 : 1 complex (K11) between 1 and PPIX is determined to be 4 × 106 M-1. Furthermore, 1 also forms a more stable complex with iron(iii) protoporphyrin IX (Fe(iii)PPIX), the K11 value for which is one order of magnitude greater than that for PPIX, indicating that 1 could be used as a recognition unit of a synthetic heme sensor. On the other hand, the formation of the stable PPIX·1 complex (supramolecular photosensitizer) prompted us to apply it to photodynamic therapy (PDT). Cell staining experiments using the supramolecular photosensitizer and evaluations of its photocytotoxicity indicate that the PDT activity of PPIX is improved as the result of the formation of a complex with 1.
Protoporphyrin IX
Cite
Citations (16)
Protoporphyrin IX
Cite
Citations (129)
Fluorescence detection may help to demarcate skin cancer from normal skin, thus to reduce the potential of incomplete treatment resulting from unawareness of tumour extension in surrounding skin. In this study we evaluated the difference between autofluorescence of basal cell carcinomas (n = 21) and the normal-appearing skin surrounding them. Referring to the difference found, a point-by-point measurement was taken from the tumour lesions outwards to the surrounding skin to locate the differentiation point of autofluorescence on the skin. Protoporphyrin IX fluorescence was measured from the same spots using the same procedure, after the tumours and the surrounding skin had been treated with topical 5-aminolevulinic acid methyl ester cream. The point-by-point measurement enabled us to locate the vanishing point of the protoporphyrin IX peak, which was compared with the differentiation point of autofluorescence to assess the utility of autofluorescence in tumour demarcation. Illuminated by 370 nm light, both the tumour and surrounding skin emitted a fluorescence with peak intensity at 455+/-3 nm. The peak intensity was 53% (18-84%) (median, range) lower in the tumours than in normal skin (p<0.001). In 78% of the measurements, the differentiation point of the autofluorescence was within 3mm of the vanishing point of the protoporphyrin IX peak. Autofluorescence may be used in BCC demarcation.
Autofluorescence
Protoporphyrin IX
Basal (medicine)
Cite
Citations (74)
Protoporphyrin IX
Cite
Citations (0)
Protoporphyrin IX dimethyl ester (PME), a dimethyl esterification of protoporphyrin IX (PpIX), exhibits higher intracellular uptake into NPC/CNE2 cells, a poorly differentiated human nasopharyngeal carcinoma, than does PpIX. Phototoxicity studies reveal PME to be a more potent photosensitizer than is PpIX, at the early and late incubation time points. Correlating phototoxicity with subcellular localization indicates that PME is a more potent photosensitizer when its primary target of photodamage is mitochondria. Also, additional targeting of lysosome enhances phototoxicity.
Phototoxicity
Protoporphyrin IX
Cite
Citations (10)
Protoporphyrin IX
Cite
Citations (25)
The greater efficacy of photodynamic therapy (PDT) depends on the selective accumulation of the photosensitizer in the cells mitochondria. Protoporphyrin IX (PpIX) is an efficient photosensitizer when administered in the form of its non-photosensitizer precursor, the 5-aminolevulinic acid. However, when administered directly, PpIX high hidrophobicity and diffuse distribution into the cells impaired PDT efficacy. Target PpIX to the cells mitochondria could improve PDT efficiency with this drug. This target delivery can be achieved with the use of drug delivery systems, such as the dendrimers. Polyamidoamine generation – 4 hydroxyl terminated dendrimer (PAMAM G4-OH) are hyberbranched polymers capable to form complexes with PpIX, increasing PpIX aqueous solubility (Patente BR 10 2012 002494 2 (2012)) and likely changing its inner cell distribution.
Protoporphyrin IX
Cite
Citations (0)
Photodynamic therapy (PDT) is an effective treatment method for various types of invasive tumors. The efficiency of PDT treatment depends, to a great extent, on optimal dosimetry of light, the photosensitizer used, and on tissue oxygenation. Fluorescence spectroscopy can be employed for measurement of drug concentration in target tissue and can provide a basis for in vivo evaluation of treatment efficiency. We have developed an integrated system that can be used to determine photosensitizer concentration in vivo based on fluorescence measurements. In our study, we performed fluorescence measurements on colon tumors of Balb/c mice in which CT26 cells were injected subcutaneously in the right flank. 5-Aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) was used as the photosensitizer. ALA was administered intraperitoneally at a dose of 200 mg/kg and PpIX fluorescence profiles were followed up to 34 h after ALA administration. Maximum fluorescence intensity was found 8 h after ALA administration. Also, we determined the relationship between PpIX concentration in colon tumor tissue of Balb/c mice and its fluorescence intensity at the peak of the spectrum (635 nm). This was used to determine the PpIX content in the target tissue as a function of time after ALA administration.
Protoporphyrin IX
Cite
Citations (3)
Photodynamic therapy (PDT) is a treatment modality for a variety of cancers. Since no ideal photosensitizer is available yet, new photosensitizers are being sought. A new concept of PDT is the use of endogenous photosensitizers. ALA is a metabolite in heme synthesis. It is a precursor of protoporphyrin IX, a potent photosensitizer. After administration of ALA it is transformed by the cells to protoporphyrin IX. The goal of our study was to examine dark toxicity of ALA and its phototoxic potential in two different human cell lines.
Protoporphyrin IX
Phototoxicity
Cite
Citations (0)
Protoporphyrin IX dimethyl ester (PME), a dimethyl esterification of protoporphyrin IX (PpIX), exhibits higher intracellular uptake into NPC/CNE2 cells, a poorly differentiated human nasopharyngeal carcinoma, than does PpIX. Phototoxicity studies reveal PME to be a more potent photosensitizer than is PpIX, at the early and late incubation time points. Correlating phototoxicity with subcellular localization indicates that PME is a more potent photosensitizer when its primary target of photodamage is mitochondria. Also, additional targeting of lysosome enhances phototoxicity.
Phototoxicity
Protoporphyrin IX
Cite
Citations (2)