Protoporphyrin IX

About: Protoporphyrin IX is a research topic. Over the lifetime, 2250 publications have been published within this topic receiving 65544 citations. The topic is also known as: PpIX.

5-Aminolaevulinic acid peptide prodrugs enhance photosensitization for photodynamic therapy.

Abstract: Intracellular porphyrin generation following administration of 5-aminolaevulinic acid (ALA) has been widely used in photodynamic therapy for a range of malignant and nonmalignant lesions. However, ALA is relatively hydrophilic and lacks stability at physiologic pH, limiting its bioavailability. We have investigated more lipophilic, uncharged ALA-peptide prodrugs based on phenylalanyl-ALA conjugates, which are water soluble and chemically stable for improving ALA delivery. Pharmacokinetics of the induced protoporphyrin IX (PpIX) were studied in transformed PAM212 keratinocyte cells and pig skin explants. The intracellular porphyrin production was substantially increased with Ac-L-Phe-ALA-Me (compound 1) and Ac-L-Phe-ALA (compound 3) compared with equimolar ALA: after 6-h incubation, the PpIX fluorescence measured using 0.01 mmol/L of compound 1 was enhanced by a factor of 5 compared with ALA. Phototoxicity results showed good correlation with PpIX levels, giving a LD50 (2.5 J/cm(2)) of 25 mu mol/L for ALA, 6 mu mol/L for 5-aminolaevulinic hexyl ester, and 2.6 mu mol/L for compound 1, which exhibited the highest phototoxicity. However, these results were stereospecific because the corresponding D-enantiomer, Ac-D-Phe-ALA-Me (compound 2), induced neither porphyrin synthesis nor phototoxicity. PpIX levels were considerably reduced when cells were incubated with compound 1 at low temperatures, consistent with active transport. In pig skin explants, compound 1 induced higher porphyrin fluorescence than ALA by a factor of 3. These results show that water-soluble peptide prodrugs of ALA can greatly increase its cellular uptake, generating more intracellular PpIX and improved tumor cell photosensitization. The derivatives are comparable in efficacy with 5-aminolaevulinic hexyl ester but less toxic and more stable at physiologic pH.

In vitro comparison of hypericin and 5-aminolevulinic acid-derived protoporphyrin IX for photodynamic inactivation of medulloblastoma cells.

Abstract: Background Hypericin (HYP) is a naturally occurring photosensitizer. Cellular uptake and photodynamic inactivation after incubation with this photosensitizer have neither been examined in medulloblastoma cells in vitro, nor compared with 5-aminolevulinic acid-derived protoporphyrin IX (5-ALA-derived PpIX).

Electron Paramagnetic Resonance Studies of the Effectiveness of Myoglobin and Its Derivatives as Photosensitizers in Singlet Oxygen Generation

Abstract: The effectiveness of myoglobin and its derivatives as photosensitizers in singlet oxygen (1O2) generation was determined by electron paramagnetic resonance (EPR) spectroscopy using a spin trapping technique. A stable nitroxide radical adduct, 2,2,6,6,-tetramethyl-4-piperidone-N-oxyl (TAN), was formed and detected by EPR. Native myoglobin and apomyoglobin exhibited no photosensitizing function, whereas hematin appeared to be a weak sensitizer. Protoporphyrin IX ring showed strong photosensitizing activity. A 1O2 quencher, N,N N′N′-tetramethylethylene diamine (TMEDA) and the combination of TMEDA and a free radical scavenger, butylated hydroxyanisole (BHA) drastically reduced the EPR signal of TAN when protoporphyrin IX solution was illuminated indicating that 1O2 was produced using protoporphyrin IX ring as a sensitizer.