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

Abstract

In this study, poly (lactic-co-glycolic) acid nanoparticles loading inorganic molybdenum octahedral cluster were used for photodynamic therapy (PDT) of ovarian cancer. )4N)2[{Mo6Br8}Br6], Cs2[{Mo6Br8}Br6] and Cs2[{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 µM. Following photo-activation, CNPs were able to generate singlet oxygen resulting in a decrease of the cellular viability, compared to non-activated conditions. Three cluster compounds, ((C4H9Nevertheless, no significant differences between IC 50 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 (IC 50 ) value near 1.8 µM 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.

From molecules to nanovectors: Current state of the art and applications of photosensitizers in photodynamic therapy

“…Cell viability was evaluated in vitro on the A2780 ovarian cancer cell line after treatment by the free or encapsulated cluster in NPs for concentrations varying from 5 to 100 µg / ml and for different incubation times (24, 48 and 72h). A strong photo-toxicity was obtained for CMIF loaded nanoparticles with a half maximal inhibitory concentration (IC 50 ) value near 1.8 µM (Brandhonneur et al, 2020). Preliminary work therefore presents the octahedral clusters of molybdenum as new PS for PDT of ovarian cancer and suggest that PLGA polymer nanoparticles constitute a delivery system suitable for targeting cells tumor.…”

Expanding the Toolbox of Octahedral Molybdenum Clusters and Nanocomposites Made Thereof: Evidence of Two-Photon Absorption Induced NIR Emission and Singlet Oxygen Production

“…46 Values are expressed in Goppert−Mayer units (1 GM = 10 −50 cm 4 s photon −1 ) and might appear low compared to carefully engineered TPA emitters like conjugated metalloporphyrins, 47 gold nanorods, 48 or Cd containing quantum dots. 49 However, we wish to state that Cs 2 Mo 6 I i 8 (OCOC 2 F 5 ) a has a low dark toxicity 7 and that the cluster structure has not yet been optimized to improve this parameter. Indeed, octahedral clusters can be easily functionalized with organic ligands, 13,23,50 and designing organic synthons able to improve cluster TPA cross section should be the next step of this research field.…”

“…Octahedral transition metal cluster based compounds of general formula A x M 6 X i 8 L a 6 (A = monovalent cation, x = 2 for M = Mo or W or x = 4 for M = Re, X i = halogen or chalcogen inner ligand, and L a = anionic apical ligand) have attracted the attention of many research groups this past decade for their abilities to emit in the red–NIR and produce singlet oxygen upon either UV–vis or X-ray irradiation. − Many studies have described their potential in cancer treatment, , bioimaging, optoelectronics, − lighting, , solar concentrators, , anticouterfeiting, oxygen sensors, − or photocatalysis . Herein, we demonstrate the ability of A 2 Mo 6 I i 8 (OCOC 2 F 5 ) a 6 (A = alkali or organic cation) to emit red–NIR light and generate singlet oxygen upon NIR excitation by a two-photon absorption (TPA) process.…”

Combining Nanotechnology and Gas Plasma as an Emerging Platform for Cancer Therapy: Mechanism and Therapeutic Implication

“…Selenium NPs, poly (lactic-co-glycolic) acid NPs with inorganic molybdenum octahedral cluster, Fe 2 O 3 NPs, PEGL NPs, chitosan copolymermagnetic NPs, poly-ε-caprolactone NPs Inhibition of cancer cell growth, cytotoxic effect on cancer cells, reduction of metastasis, decrease of cancer cell viability and cytotoxicity, increased the intracellular ROS/RNS, diminution of tumor volume[194][195][196][197][198][199] Colon cancer Albumin NPs, chitosan NPs, perfluorooctylbromide-porphyrin grafted lipid NPs, biosynthesized silver NPs, superparamagnetic iron oxide coated with mesenchymal stem cell, silver and gold NPs, mesoporous silica NPs coated with folic acid chitosan-glycine complex, hydroxyapatite NPs coated with gum Arabic, PLGA NPs co-loaded with 5-fluorouracil and perfluorocarbonEnhancement of cancer cells killing; improved antitumor efficacy; prevention of tumor growth and metastasis; decrement of tumor volume; enhancement of photodynamic effects against cancer cells (by increasing oxidative stress); induction of apoptosis (overexpression of caspase-3, caspase-9, bid, and Bax); reduction of immune system response and systemic side effects; fragmentation of DNA in cancer cells; increase in antimitotic effects[200][201][202][203][204][205][206][207] Glioblastoma Silver NPs, lanthanum oxide NPs, transferrinconjugated porous silicon NPs, high-Z metal NPs, PEI surface-functionalized mesoporous silica NPs, PLGA NPs coated with polyvinyl alcohol and Poloxamer188, magnetic iron oxide NPs loaded trimethoxysilylpropyl-ethylenediamine triacetic acid, polymerized human serum albumin NPs, PEI-PEG-magnetic iron oxide NPs…”