Protoporphyrin IX is an important porphyrin compound in the heme biosynthetic pathway and is commonly used in photodynamic therapy[1]. Protoporphyrin IX binds with iron ions to form ferrous protoporphyrin, which then combines with globin to generate hemoglobin, thereby maintaining oxygen transport and cellular respiration functions[2]. In photodynamic therapy, Protoporphyrin IX primarily serves as a photosensitizer, capable of absorbing specific wavelengths of light and generating reactive oxygen species[3]. In addition, the fluorescence imaging of Protoporphyrin IX (excitation wavelength 488nm, emission wavelength 620nm) can also be utilized to improve surgical outcomes[4].
In vitro, Protoporphyrin IX (10-30μM) treatment of SK-MEL-2 melanoma cells and human normal melanocytes (HNM) for 48 hours significantly promotes melanin synthesis, increases tyrosinase activity, and upregulates the expression levels of MITF, tyrosinase, TRP-1, and TRP-2, while also promoting dendrite formation and melanosome transport in melanocytes[5]. The novel conjugate CH−PPIX (0.005%, w/v) formed by Protoporphyrin IX and chitosan oligosaccharides (CH) exhibits 100% inhibitory efficiency against Penicillium digitatum under visible light irradiation. This conjugate exerts antifungal effects through the generation of singlet oxygen, leading to spore uptake and photoinduced membrane damage[6].
In vivo, Protoporphyrin IX (3.5mg/kg) was administered to mice via a single intraperitoneal injection or daily injections for 5 consecutive days. Two hours after a single dose, the accumulation of porphyrins in the mouse liver peaked. After five doses, Protoporphyrin IX accumulation induced oxidative stress, causing severe liver damage and impairing the antioxidant system[7]. Protoporphyrin IX-modified oxidized mesoporous carbon nanospheres (1mg/kg) were injected into APP/PS1 transgenic mice via the tail vein and activated by focused ultrasound. These nanospheres could effectively cross the blood-brain barrier (BBB), significantly inhibit Tau protein phosphorylation and β-amyloid (Aβ) aggregation, and improve cognitive function in mice[8].
References:
[1] Juzenas P, Juzeniene A, Stakland S, et al. Photosensitizing effect of protoporphyrin IX in pigmented melanoma of mice. Biochem Biophys Res Commun. 2002 Sep 27;297(3):468-72.
[2] Kiening M, Lange N. A Recap of Heme Metabolism towards Understanding Protoporphyrin IX Selectivity in Cancer Cells. Int J Mol Sci. 2022 Jul 19;23(14):7974.
[3] Hussain Z, Qi Q, Zhu J, Anderson KE, et al. Protoporphyrin IX-induced phototoxicity: Mechanisms and therapeutics. Pharmacol Ther. 2023 Aug;248:108487.
[4] Valdes PA, Millesi M, Widhalm G, et al. 5-aminolevulinic acid induced protoporphyrin IX (ALA-PpIX) fluorescence guidance in meningioma surgery. J Neurooncol. 2019 Feb;141(3):555-565.
[5] Lv J, An X, Jiang S, Yang Y, et al. Protoporphyrin IX Stimulates Melanogenesis, Melanocyte Dendricity, and Melanosome Transport Through the cGMP/PKG Pathway. Front Pharmacol. 2020 Sep 11;11:569368.
[6] Dibona-Villanueva L, Fuentealba D. Protoporphyrin IX-Chitosan Oligosaccharide Conjugate with Potent Antifungal Photodynamic Activity. J Agric Food Chem. 2022 Aug 3;70(30):9276-9282.
[7] Afonso S, Vanore G, Batlle A. Protoporphyrin IX and oxidative stress. Free Radic Res. 1999 Sep;31(3):161-70.
[8] Xu M, Zhou H, Liu Y, Sun J, et al. Ultrasound-Excited Protoporphyrin IX-Modified Multifunctional Nanoparticles as a Strong Inhibitor of Tau Phosphorylation and β-Amyloid Aggregation. ACS Appl Mater Interfaces. 2018 Oct 3;10(39):32965-32980.