Low Blue Dose Photodynamic Therapy with Porphyrin-Iron Oxide Nanoparticles Complexes: In Vitro Study on Human Melanoma Cells.

Iulia Lungu,Tatiana Tozar,Florian Dumitrache,Mihai Boni,Valentin-Adrian Maraloiu,Roua Gabriela Popescu,Ecaterina Andronescu,Claudiu Fleaca,Anca Dinischiotu,Ana-Maria Udrea,Madalina Andreea Badea,Angela Staicu,Simona Nistorescu,Mihaela Balas

doi:10.3390/pharmaceutics13122130

Abstract

The purpose of this study was to investigate the effectiveness in photodynamic therapy of iron oxide nanoparticles (γ-Fe2O3 NPs), synthesized by laser pyrolysis technique, functionalized with 5,10,15,20-(Tetra-4-sulfonatophenyl) porphyrin tetraammonium (TPPS) on human cutaneous melanoma cells, after only 1 min blue light exposure. The efficiency of porphyrin loading on the iron oxide nanocarriers was estimated by using absorption and FTIR spectroscopy. The singlet oxygen yield was determined via transient characteristics of singlet oxygen phosphorescence at 1270 nm both for porphyrin functionalized nanoparticles and rose bengal used as standard. The irradiation was performed with a LED (405 nm, 1 mW/cm2) for 1 min after melanoma cells were treated with TPPS functionalized iron oxide nanoparticles (γ-Fe2O3 NPs_TPPS) and incubated for 24 h. Biological tests revealed a high anticancer effect of γ-Fe2O3 NPs_TPPS complexes indi-cated by the inhibition of tumor cell proliferation, reduction of cell adhesion, and induction of cell death through ROS generated by TPPS under light exposure. The biological assays were combined with the pharmacokinetic prediction of the porphyrin.

Highlights

Melanoma is the most lethal type of skin cancer and the third form of malignancy encountered between the ages of 15 to 39 years, with an incidence constantly increasing.Among the risk factors involved in the evolution of aggressive skin the malignant tumor are found: family history, ultraviolet (UV) radiation exposure, or variations in pigmentation genes [1,2,3]
The X-ray diffractogram (Figure 3) of the synthesized powder sample indicated its nanophase feature and the crystalline structure can be assigned to γ-Fe2 O3 /Fe3 O4 phases: the position of theoretical diffraction peaks is illustrated with diamonds
In cells that were not exposed to LED light, we found that the GSH content of treated cells was almost similar to the one measured in control cells

Summary

Introduction

Melanoma is the most lethal type of skin cancer and the third form of malignancy encountered between the ages of 15 to 39 years, with an incidence constantly increasing. Among the risk factors involved in the evolution of aggressive skin the malignant tumor are found: family history, ultraviolet (UV) radiation exposure, or variations in pigmentation genes [1,2,3]. The pathogenic mechanism of melanoma involves two cell subpopulations in the epidermis, called melanocytes and keratinocytes. As a result of UV exposure, skin keratinocytes increase melanin generation by producing the melanocyte-stimulating hormone (MSH) that binds the melanocortin receptor 1 (MC1R) found on melanocytes surface. The melanocytes transfer melanin to surrounding keratinocytes and protect the living cells. The melanoma risk appears as a cause of long exposure of the nuclei to UV damage and accumulation of the mutations in sensitive regions [3,4,5,6,7]

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