期刊
CANCERS
卷 11, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/cancers11111760
关键词
photodynamic therapy; lipid nanoparticles; drug delivery system; tumor vectorization; verteporfin; ovarian carcinomatosis; spheroids
类别
资金
- Canceropole Lyon Auvergne Rhone-Alpes, Oncostarter program
- French National Research Agency [ANR-17-EURE-0003]
- Glyco@Alps Investissement d'avenir program [ANR-15-IDEX-02]
- France Live Imaging (FLI-Grenoble)
- France Live Imaging (French program Investissement d'Avenir)
- France Live Imaging (grant Infrastructure d'avenir en Biologie Sante) [ANR-11-INBS-0006]
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.
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