Molybdenum-Iodine Cluster Loaded Polymeric Nanoparticles Allowing a Coupled Therapeutic Action with Low Side Toxicity for Treatment of Ovarian Cancer.

The ability of cancer cells to develop resistance to anti-cancer drugs, known as multidrug resistance, remains a major cause of tumor recurrence and cancer metastasis. This work explores the double mechanism of toxicity of (D, L-lactide-co-glycolide) acid (PLGA) nanoparticles encapsulating a molybdenum cluster compound, namely Cs2[{Mo6I8}(OOCC2F5)6] (CMIF). Hemocompatibility and biocompatibility assays show the safe potential of CMIF loaded nanoparticles (CNPs) as delivery systems intended for tumor targeting for PDT of ovarian cancer with a slight hemolytic activity and a lack of toxicity up to 50 µM CMIF concentration. Cellular uptake shows a preferential uptake of CNPs in lysosomes, which is not interfering with CMIF activity. The double mechanism of CNPs consists in a production of ROS and a DNA damage activity, from 5 µM and 0.5 µM respectively (CMIF concentration). The cellular death mechanism comprises 80% of necrosis and 20% of direct apoptosis by direct DNA damages. This work confirms CMIF loaded PLGA nanoparticles as an efficient and relevant delivery system for PDT.

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

Photodynamic therapy (PDT) is a concept based on a selective activation by light of drugs called photosensitizers (PS) leading to reactive oxygen species production responsible for cell destruction. Mechanisms of photodynamic reaction and cell photo-destruction following direct or indirect mechanisms will be presented as well as PS classification, from first generation molecules developed in the 1960 s to third generation vectorized PS with improved affinity for tumor cells. Many clinical applications in dermatology, ophthalmology, urology, gastroenterology, gynecology, neurosurgery and pneumology reported encouraging results in human tumor management. However, this interesting technique needs improvements that are currently investigated in the field of PS excitation by the design of new PS intended for two-photon excitation or for X-ray excitation. The former excitation technique is allowing better light penetration and preservation of healthy tissues while the latter is combining PDT and radiotherapy so that external light sources are no longer needed to generate the photodynamic effect. Nanotechnology can also improve the PS to reach the tumor cells by grafting addressing molecule and by increasing its aqueous solubility and consequently its bioavailability by encapsulation in synthetic or biogenic nanovector systems, ensuring good drug protection and targeting. Co-internalization of PS with magnetic nanoparticles in multifunctional vectors or stealth nanoplatforms allows a theranostic anticancer approach. Finally, a new category of inorganic PS will be presented with promising results on cancer cell destruction.

PLGA nanoparticles embedding molybdenum cluster salts: Influence of chemical composition on physico-chemical properties, encapsulation efficiencies, colloidal stabilities and in vitro release.

We present a screening of poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles embedding a series of inorganic molybdenum octahedral clusters intended for photodynamic therapy (PDT) of cancer. Three cluster compounds from 2 cluster units, [{Mo6Br8}Br6]2- and [{Mo6I8}(OOC2F5)6]2- were studied. [{Mo6Br8}Br6]2-cluster units are found in the soluble ternary salt Cs2[{Mo6Br8}Br6] (CMB) prepared by solid state chemistry at high temperature. In solution Cs+ cations are replaced by tetrabutyl ammonium cations (C4H9)4N+) to form the salt ((C4H9)4N)2[{Mo6Br8}Br6] (TBA2). [{Mo6I8}(OOC2F5)6]2- was prepared combining solid state and solution chemistries; it is paired with Cs+ cations to form Cs2[{Mo6I8}(OOC2F5)6] (CMIF). All tested cluster-based salts could efficiently be incorporated in PLGA nanoparticles as seen with encapsulation efficiencies always higher than 60%. Cluster loaded nanoparticles (CNPs) freshly prepared by solvent displacement method showed spherical shapes, zeta potential values between -20 and -47 mV, polydispersity index in the range 0.123-0.167 and sizes in the range 75-150 nm according to the cluster compound and the polymer-to-cluster mass ratio (P/C), suggesting a good cellular uptake. CNPs colloidal stability was maintened for 3 months when they were stored refrigerated and protected from light but the chemical stability was shorter, i.e. 4 weeks, 1 week and 1 day for CMIF, TBA2 and CMB, respectively, CMIF penta-fluoropropionate apical ligands being less rapidly substituted by hydroxyles groups than TBA2 and CMB halogen apical ligands. FT-IR analysis revealed the lack of strong chemical interaction between cluster compounds and polymer within the nanoparticles. An interesting quick cluster in vitro release driven by diffusion outside the nanoparticles porous matrix was observed for all cluster compounds when P/C ratio was ≤2.5 and only a higher P/C ratio not studied in this work (i.e. >5) could significantly affect the release of the encapsulated cluster compound. Photophysical properties of cluster compounds were preserved following PLGA incorporation. This work presents PLGA nanoparticles as a stable and efficient cluster compound delivery systems for further in vitro and vivo evaluations in cancer models.

Molybdenum cluster loaded PLGA nanoparticles: An innovative theranostic approach for the treatment of ovarian cancer.

We evaluate poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles embedding inorganic molybdenum octahedral cluster for photodynamic therapy of cancer (PDT). Tetrabutyl ammonium salt of Mo6Br14 cluster unit, (TBA)2Mo6Br14, presents promising photosensitization activity in the destruction of targeted cancer cells. Stable cluster loaded nanoparticles (CNPs) were prepared by solvent displacement method showing spherical shapes, zeta potential values around -30 mV, polydispersity index lower than 0.2 and sizes around 100 nm. FT-IR and DSC analysis revealed the lack of strong chemical interaction between the cluster and the polymer within the nanoparticles. In vitro release study showed that (TBA)2Mo6Br14 was totally dissolved in 20 min, while CNPs were able to control the release of encapsulated cluster. In vitro cellular viability studies conducted on A2780 ovarian cancer cell line treated up to 72 h with cluster or CNPs did not show any sign of toxicity in concentrations up to 20 µg/ml. This concentration was selected for photo-activation test on A2780 cells and CNPs were able to generate oxygen singlet resulting in a decrease of the cellular viability up to 50%, respectively compared to non-activated conditions. This work presents (TBA)2Mo6Br14 as a novel photosensitizer for PDT and suggests PLGA nanoparticles as an efficient delivery system intended for tumor targeting.

Efficient active waveguiding properties of Mo6 nano-cluster-doped polymer nanotubes.

We investigate 1D nanostructures based on a Mo6@SU8 hybrid nanocomposite in which photoluminescent Mo6 clusters are embedded in the photosensitive SU8 resist. Tens of micrometers long Mo6@SU8-based tubular nanostructures were fabricated by the wetting template method, enabling the control of the inner and outer diameter to about 190 nm and 240 nm respectively, as supported by structural and optical characterizations. The image plane optical study of these nanotubes under optical pumping highlights the efficient waveguiding phenomenon of the red luminescence emitted by the clusters. Moreover, the wave vector distribution in the Fourier plane determined by leakage radiation microscopy gives additional features of the emission and waveguiding. First, the anisotropic red luminescence of the whole system can be attributed to the guided mode along the nanotube. Then, a low-loss propagation behavior is evidenced in the Mo6@SU8-based nanotubes. This result contrasts with the weaker waveguiding signature in the case of UV210-based nanotubes embedding PFO (poly(9,9-di-n-octylfluorenyl-2,7-diyl)). It is attributed to the strong reabsorption phenomenon, owing to overlapping between absorption and emission bands in the semi-conducting conjugated polymer PFO. These results make this Mo6@SU8 original class of nanocomposite a promising candidate as nanosources for submicronic photonic integration.

Phosphorescent columnar hybrid materials containing polyionic inorganic nanoclusters.

The ternary polyionic inorganic compound Cs2Mo6Br14 and 18-crown-6 ethers bearing two o-terphenyl units have been combined to design phosphorescent columnar liquid crystalline hybrid materials. The obtained host-guest complexes are very stable even at high temperatures. Depending on their surrounding atmosphere, these hybrids switch reversibly from a high-to-low luminescence state and show a very stable emission intensity up to 140 °C.

Preparation of colloidal solution of silica encapsulating cyanobiphenyl unit-capped ZnO QD emitting in the blue region.

The encapsulation of ZnO nanoparticles (5 nm) coated by cyanobiphenyl units by the sol-gel technique leads to spherical ZnO@SiO2 nanoparticles displaying blue emission under UV excitation.