4.7 Article

Molybdenum cluster loaded PLGA nanoparticles as efficient tools against epithelial ovarian cancer

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 592, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ijpharm.2020.120079

Keywords

PLGA nanopartide; Molybdenum dusters; Ovarian cancer cell line A2780; Photodynamic therapy; Singlet oxygen

Funding

  1. Rennes Metropole
  2. European Union (CPER-FEDER 2015-2020, project CAPHTER)

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Poly (lactic-co-glycolic) acid nanoparticles loaded with inorganic molybdenum octahedral clusters were used for photodynamic therapy of ovarian cancer. Among the studied cluster compounds, CMIF-loaded nanoparticles showed higher internalization efficiency in A2780 ovarian cancer cell line and significant decrease in cellular viability following photo-activation.
In this study, poly (lactic-co-glycolic) acid nanoparticles loading inorganic molybdenum octahedral cluster were used for photodynamic therapy (PDT) of ovarian cancer. Three cluster compounds, ((C4H9)(4)N)(2)[{Mo6Br8}Br-6], Cs-2[{Mo6Br8}Br-6] and Cs-2[{Mo6I8}(OOC2F5)(6)] denoted TMB, CMB and CMIF were studied following their incorporation in nanoparticles by a nanoprecipitation method. All resulting nanoparticles exhibited physico-chemical characteristics such as size and zeta potential compatible with cellular uptake. All cluster compounds tested were shown to produce singlet oxygen in vitro once released from their nanoparticulate system. Confocal images showed an internalisation of cluster loaded nanoparticles (CNPs) in A2780 ovarian cancer cell line, more efficient with CMIF compared to CMB or TMB loaded nanoparticles. In vitro cellular viability studies conducted on A2780 cell line treated with non activated CNPs did not show any sign of toxicity for concentrations up to 15 mu M. Following photo-activation, CNPs were able to generate singlet oxygen resulting in a decrease of the cellular viability, compared to non-activated conditions. Nevertheless, no significant differences between IC50 with or without photo-activation were observed with TMB and CMB CNPs while for CMIF loaded nanoparticles, the photo-activation led to a significant decrease of cellular viability compared to the non activated condition and this decrease was independant of the P/C ratio. The strong photo-toxicity obtained for CMIF loaded nanoparticles with a P/C ratio of 2.5, as shown with half maximal inhibitory concentration (IC50) value near 1.8 mu M suggests that PLGA nanoparticles seem to be efficient delivery systems intended for tumor management and that CMIF can be further investigated as photosensitizer for PDT of ovarian cancer.

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