Design of hybrid protein-coated magnetic core-mesoporous silica shell nanocomposites for MRI and drug release assessed in a 3D tumor cell model

International audienceIn this work, we describe the design and the use of a novel theranostic hybrid nanocomposite made of an iron oxide core and a mesoporous silica shell (IO@MS) of ca. 30 nm coated by human serum albumin (HSA) layer for magnetic resonance imaging and drug delivery applications. The porosity of IO@MS nanoparticles was loaded with an antitumoral drug, Doxorubicin (Dox) reaching a high drug loading capacity (DLC) of 34 w%. To entrap the drug, a tight HSA coating held via isobutyramide (IBAM) binders was deposited. We show that this protein nanoassembly entraps the drugs efficiently and behaves as an innovative enzyme-sensitive gatekeeper that is degraded upon protease action. Finally we assess the Dox release in a 3D cell model via confocal imaging and its cytotoxicity is shown by growth inhibition studies on liver cancer cell spheroid

Conductive and Cytocompatible Poly(3,4)ethylene-dioxythiophene:poly(styrenesulfonate) Hierarchical Porous Materials: From Liquid to Solid Foams

International audiencePoly(3,4)ethylene-dioxythiophene (PEDOT), mainly associated with poly(styrenesulfonate) (PSS), is widely used to create thin conductive films or, more recently, conductive 3D porous materials as scaffolds for tissue engineering. Such conductive materials allow the direct delivery of electrical, electrochemical, and electromechanical stimuli to cells. Typically, surfactants are combined with the PEDOT:PSS dispersion to design conductive films by gelation. To the best of our knowledge, no foams have been reported using PEDOT:PSS/surfactant mixtures and a simple drying process. In this article, to develop a cytocompatible and conductive 3D porous material by a simple process, a PEDOT:PSS/cationic surfactant mixture was used to design solid foams by simple foaming followed by a drying step. We exploit the electrostatic interactions between negatively charged commercial PEDOT:PSS and positively charged N-octyltrimethylammonium bromide (C8TAB) surfactant to develop conductive solid foams via the solidification of liquid foams. The stable and homogeneous liquid PEDOT:PSS/C8TAB foams were dried to obtain solid and conductive foams with a high conductivity of 2.05 ± 0.80 S/cm. The high conductivity of the bulk PEDOT:PSS/C8TAB thin film, at 17 ± 4 S/cm, confirmed a doping effect of C8TAB. This increased conductivity in the presence of the surfactants is probably due to an increased interpenetration of the PEDOT:PSS particles during film formation. The resulting foams are highly conductive and noncytotoxic, allowing the proliferation of murine fibroblasts. These foams have great potential for biomedical applications

Physicochemical and Mechanical Properties of Premixed Calcium Silicate and Resin Sealers

The aim of the present in vitro study was to evaluate specific mechanical and physicochemical properties of two calcium silicate based sealers, (AH Plus Bioceramic “AHPB”; Well-Root ST “WRST”), and a conventional resin sealer (AH Plus “AHP”). These aims were accomplished by assessing the porosity, pH, compression strength, roughness, wettability and cell attachment of the tested materials. The results were compared statistically using the one-way ANOVA test. Higher pH values were obtained in both AHPB and WRST compared to AHP at 3, 24 and 72 h (p p p < 0.05). The removal of calcium silicates may be quite tricky during endodontic retreatment. In conclusion, considering the limitations of the present in vitro study, both calcium silicate sealers demonstrated good physicochemical properties. However, the lower compression strength and modulus of AHPB may facilitate its removal and make the retreatment procedures considerably easier

Impacts of Resveratrol and Pyrogallol on Physicochemical, Mechanical and Biological Properties of Epoxy-Resin Sealers

This study aimed at evaluating the physicochemical and biological properties of experimental epoxy-resin sealers containing polyphenols such as resveratrol and pyrogallol. A conventional epoxy resin (OB) was modified by adding different concentrations of resveratrol (RS) or pyrogallol (PY) to its composition. Antibacterial and antioxidant activities, mechanical properties, along with wettability and morphological changes were investigated. The results were statistically analyzed using ANOVA and multiple comparison tests (&alpha; = 0.05). The incorporation of the tested polyphenols into the epoxy resin enhanced its mechanical properties. PY demonstrated much better antioxidant and antibacterial activities than RS, which were associated with a higher release of PY. In contrast, PY showed a higher cytotoxicity than OB and OB doped with RS. OB containing PY presented a rougher surface and higher water absorption than OB doped with RS. Both tested polyphenols caused no notable changes to the overall porosity of OB. Resveratrol and pyrogallol may not only influence the morphology and mechanical properties of epoxy-resin sealers, but could also enhance antioxidant activity and antibacterial effects against Enterococcus faecalis. Most epoxy-resin sealers currently available in the market can be considered as &ldquo;passive&rdquo; materials. Thus, doping their composition with specific polyphenols may be a suitable strategy to confer some antibacterial properties, antioxidant potential, along with improvement of some mechanical properties

Effect of the Size and Shape of Dendronized Iron Oxide Nanoparticles Bearing a Targeting Ligand on MRI, Magnetic Hyperthermia, and Photothermia Properties—From Suspension to In Vitro Studies

Functionalized iron oxide nanoparticles (IONPs) are increasingly being designed as a theranostic nanoplatform combining specific targeting, diagnosis by magnetic resonance imaging (MRI), and multimodal therapy by hyperthermia. The effect of the size and the shape of IONPs is of tremendous importance to develop theranostic nanoobjects displaying efficient MRI contrast agents and hyperthermia agent via the combination of magnetic hyperthermia (MH) and/or photothermia (PTT). Another key parameter is that the amount of accumulation of IONPs in cancerous cells is sufficiently high, which often requires the grafting of specific targeting ligands (TLs). Herein, IONPs with nanoplate and nanocube shapes, which are promising to combine magnetic hyperthermia (MH) and photothermia (PTT), were synthesized by the thermal decomposition method and coated with a designed dendron molecule to ensure their biocompatibility and colloidal stability in suspension. Then, the efficiency of these dendronized IONPs as contrast agents (CAs) for MRI and their ability to heat via MH or PTT were investigated. The 22 nm nanospheres and the 19 nm nanocubes presented the most promising theranostic properties (respectively, r2 = 416 s−1·mM−1, SARMH = 580 W·g−1, SARPTT = 800 W·g−1; and r2 = 407 s−1·mM−1, SARMH = 899 W·g−1, SARPTT = 300 W·g−1). MH experiments have proven that the heating power mainly originates from Brownian relaxation and that SAR values can remain high if IONPs are prealigned with a magnet. This raises hope that heating will maintain efficient even in a confined environment, such as in cells or in tumors. Preliminary in vitro MH and PTT experiments have shown the promising effect of the cubic shaped IONPs, even though the experiments should be repeated with an improved set-up. Finally, the grafting of a specific peptide (P22) as a TL for head and neck cancers (HNCs) has shown the positive impact of the TL to enhance IONP accumulation in cells

Bioconjugation studies of an EGF-R targeting ligand on dendronized iron oxide nanoparticles to target head and neck cancer cells

A major challenge in nanomedicine is designing nanoplatforms (NPFs) to selectively target abnormal cells to ensure early diagnosis and targeted therapy. Among developed NPFs, iron oxide nanoparticles (IONPs) are good MRI contrast agents and can be used for therapy by hyperthermia and as radio-sensitizing agents. Active targeting is a promising method for selective IONPs accumulation in cancer tissues and is generally performed by using targeting ligands (TL). Here, a TL specific for the epidermal growth factor receptor (EGFR) is bound to the surface of dendronized IONPs to produce nanostructures able to specifically recognize EGFR-positive FaDu and 93-Vu head and neck cancer cell lines. Several parameters were optimized to ensure a high coupling yield and to adequately quantify the amount of TL per nanoparticle. Nanostructures with variable amounts of TL on the surface were produced and evaluated for their potential to specifically target and be thereafter internalized by cells. Compared to the bare NPs, the presence of the TL at the surface was shown to be effective to enhance their internalization and to play a role in the total amount of iron present per cell. Keywords: Active targeting, head cancer; Bioconjugation; Coupling; Iron oxide; Magnetic Nanoparticles; Neck cancer; Peptide 22

Evaluation of the Active Targeting of Melanin Granules after Intravenous Injection of Dendronized Nanoparticles

The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using magnetic resonance imaging (MRI) and planar scintigraphy through [177Lu]Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles (DPs) and hepatobiliary and urinary excretions. Little tumor uptake could be highlighted after intravenous injection probably as a consequence of the negatively charged DOTAGA-derivatized shell, which reduces the diffusion across the cells' membrane. Planar scintigraphy images demonstrated a moderate specific tumor uptake of melanoma-targeted [177Lu]Lu-NPs10@D1_ICF_DOTAGA at 2 h post-intravenous injection (pi), and the highest tumor uptake of the control probe [177Lu]Lu-NPs10@D1_DOTAGA at 30 min pi, probably due to the enhanced permeability and retention effect. In addition, ex vivo confocal microscopy studies showed a high specific targeting of human melanoma samples impregnated with NPs10@D1_ICF_Alexa647_ DOTAGA