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Open AccessArticle

Verteporfin-Loaded Lipid Nanoparticles Improve Ovarian Cancer Photodynamic Therapy In Vitro and In Vivo

1
Institute for Advanced Biosciences, Institut National de la Santé Et de la Recherche Médicale INSERM U1209, Centre National de la Recherche Scientifique CNRS UMR5309, Université Grenoble Alpes, F-38000 Grenoble, France
2
Centre Hospitalier Universitaire CHU Grenoble Alpes, Université Grenoble Alpes, F-38000 Grenoble, France
3
Centre National de la Recherche Scientifique CNRS UMR5250, Département de Chimie Moléculaire, Université Grenoble Alpes, F-38000 Grenoble, France
4
Commissariat à l’Energie atomique et aux energies alternatives CEA, Laboratoire d’électronique et de technologie de l’information, Département Technologies pour la Biologie et la Santé LETI-DTBS, Université Grenoble Alpes, F-38000 Grenoble, France
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Cancers 2019, 11(11), 1760; https://doi.org/10.3390/cancers11111760
Received: 17 September 2019 / Revised: 24 October 2019 / Accepted: 5 November 2019 / Published: 8 November 2019
(This article belongs to the Special Issue Cancer Nanomedicine)
Advanced ovarian cancer is the most lethal gynecological cancer, with a high rate of chemoresistance and relapse. Photodynamic therapy offers new prospects for ovarian cancer treatment, but current photosensitizers lack tumor specificity, resulting in low efficacy and significant side-effects. In the present work, the clinically approved photosensitizer verteporfin was encapsulated within nanostructured lipid carriers (NLC) for targeted photodynamic therapy of ovarian cancer. Cellular uptake and phototoxicity of free verteporfin and NLC-verteporfin were studied in vitro in human ovarian cancer cell lines cultured in 2D and 3D-spheroids, and biodistribution and photodynamic therapy were evaluated in vivo in mice. Both molecules were internalized in ovarian cancer cells and strongly inhibited tumor cells viability when exposed to laser light only. In vivo biodistribution and pharmacokinetic studies evidenced a long circulation time of NLC associated with efficient tumor uptake. Administration of 2 mg.kg−1 free verteporfin induced severe phototoxic adverse effects leading to the death of 5 out of 8 mice. In contrast, laser light exposure of tumors after intravenous administration of NLC-verteporfin (8 mg.kg−1) significantly inhibited tumor growth without visible toxicity. NLC-verteporfin thus led to efficient verteporfin vectorization to the tumor site and protection from side-effects, providing promising therapeutic prospects for photodynamic therapy of cancer.
Keywords: photodynamic therapy; lipid nanoparticles; drug delivery system; tumor vectorization; verteporfin; ovarian carcinomatosis; spheroids photodynamic therapy; lipid nanoparticles; drug delivery system; tumor vectorization; verteporfin; ovarian carcinomatosis; spheroids
MDPI and ACS Style

Michy, T.; Massias, T.; Bernard, C.; Vanwonterghem, L.; Henry, M.; Guidetti, M.; Royal, G.; Coll, J.-L.; Texier, I.; Josserand, V.; Hurbin, A. Verteporfin-Loaded Lipid Nanoparticles Improve Ovarian Cancer Photodynamic Therapy In Vitro and In Vivo. Cancers 2019, 11, 1760.

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