Volume 3, Issue 2, Pages 303-322 (August 2017) Maghemite-nanoMIL-100(Fe) Bimodal Nanovector as a Platform for Image-Guided Therapy  Saad Sene, M. Teresa Marcos-Almaraz, Nicolas Menguy, Joseph Scola, Jeanne Volatron, Richard Rouland, Jean-Marc Grenèche, Sylvain Miraux, Clotilde Menet, Nathalie Guillou, Florence Gazeau, Christian Serre, Patricia Horcajada, Nathalie Steunou  Chem  Volume 3, Issue 2, Pages 303-322 (August 2017) DOI: 10.1016/j.chempr.2017.06.007 Copyright © 2017 Elsevier Inc. Terms and Conditions

Chem 2017 3, 303-322DOI: (10.1016/j.chempr.2017.06.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Maghemite NPs (A) High-resolution TEM image of γFe2O3 NPs. (B) FTIR spectra of γFe2O3 and γFe2O3-cit NPs. See also Figure S2. Chem 2017 3, 303-322DOI: (10.1016/j.chempr.2017.06.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 2 Surface Charge of MIL-100(Fe) and USPIO NPs Evolution of the ζ potential with pH for (A) γFe2O3 and MIL-100(Fe) and (B) γ-Fe2O3-cit and MIL-100(Fe). Chem 2017 3, 303-322DOI: (10.1016/j.chempr.2017.06.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 3 XRD Pattern of MIL/USPIO-cit(10) A structureless refinement was first performed for maghemite; the scaling factor was then fixed before profile matching for MIL-100(Fe) (λCu = 1.5406 Å). See also Figure S8. Chem 2017 3, 303-322DOI: (10.1016/j.chempr.2017.06.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 4 TEM Characterization of MIL/USPIO(10) and MIL/USPIO-cit(10) Nano-objects TEM bright-field observations of (A and B) MIL/USPIO(10) and (C–F) MIL/USPIO-cit(10). (A and B) MIL-100(Fe) NPs are covered by γ-Fe2O3 particles (A), as confirmed by high-resolution imaging (B). (C) γ-Fe2O3-cit aggregates (black solid arrow) and MIL/USPIO-cit (black dotted arrow) are simultaneously present on the carbon grids. (D) MIL-100(Fe) NPs are coated by γ-Fe2O3-cit NPs. (E and F) A network of MIL/USPIO-cit(10) nano-objects. MIL-100(Fe) NPs are covered by γ-Fe2O3-cit particles (E), as confirmed by high-resolution imaging (F). Insets of (B) and (F): the fast Fourier transform related to the crystalline particle is coherent with the inverse-spinel structure described in the cubic cell with a = 8.34 Å. See also Figures S9–S11. Chem 2017 3, 303-322DOI: (10.1016/j.chempr.2017.06.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 5 TEM Characterization of MIL/USPIO-cit(1) at Different pH TEM images of MIL/USPIO-cit(1) at (A and B) pH 3.5 and (C and D) pH 7 (PBS-BSA medium). See also Figure S12. Chem 2017 3, 303-322DOI: (10.1016/j.chempr.2017.06.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 6 Colloidal Stability of MIL/USPIO-cit Nano-objects in Physiologic Serum Conditions DLS of the MIL/USPIO-cit (10 and 1 wt %) nano-objects in 0.01 M PBS (blue line) and 0.01 M PBS with 5.4% w/v BSA (orange line) at 37°C and 100 rpm. The evolution of the average particle diameter for (A) MIL/USPIO-cit(10) and (B) MIL/USPIO-cit(1) and the polydispersity index (PdI) over a time period of 24 hr for (C) MIL/USPIO-cit(10) and (D) MIL/USPIO-cit(1) are shown. Chem 2017 3, 303-322DOI: (10.1016/j.chempr.2017.06.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 7 Relaxometric and Magnetic Properties of MIL/USPIO-cit Nano-objects (A) T2-weighted MRI images extracted from T2 measurements compare the T2 contrast from the MIL/USPIO-cit(10) nano-objects with Fe concentration ranging from 0 (control) to ∼5.8 mM. (B) Transverse relaxation rates (1/T2, s−1) as a function of iron concentration for the γ-Fe2O3-cit, MIL-100(Fe), MIL/USPIO-cit(10), and MIL/USPIO-cit(1) prepared in PBS-BSA solution at pH 7.4. (C) Separation of MIL/USPIO-cit(10) and MIL/USPIO-cit(1) from solution under an external magnetic field. (D) Magnetization curve of MIL/USPIO-cit(1) at 300 K (solid black line) and a Langevin fit (dotted red line). See also Table S1 and Figures S13–S15. Chem 2017 3, 303-322DOI: (10.1016/j.chempr.2017.06.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 8 Drug Delivery, Cytotoxicity, and Anti-cancer Efficiency of MIL/USPIO-cit (A) Doxorubicin delivery under simulated physiologic conditions (PBS, 37°C) from MIL-100(Fe), MIL/USPIO-cit(1), and MIL/USPIO-cit(10). (B) Normalized cell viability obtained after incubation with pure nano-objects (i.e., MIL-100(Fe) and MIL/USPIO-cit(10)) and nano-objects loaded with DOX (i.e., DOX@MIL-100(Fe) and DOX@MIL/USPIO-cit(10)) at 100, 50, and 10 μg/mL and with free DOX at 6, 3, and 0.6 μM. (C) Optical micrographs of cells incubated with DOX@MIL/USPIO-cit(10) at 100, 50, and 10 μg/mL and control cells. All experiments were carried out in triplicate. Scale bars, 20 μm. See also Figure S16. Chem 2017 3, 303-322DOI: (10.1016/j.chempr.2017.06.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 9 3D T2*-Weighted Gradient Echo Images of the Mouse Abdomen before and after Injection of Contrast Agent Liver and spleen locations are indicated in the last column. See also Figure S17. Chem 2017 3, 303-322DOI: (10.1016/j.chempr.2017.06.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Scheme 1 Trimers of Fe(III) Octahedra Assembled with Trimesic Acid Leading to the Formation of the MIL-100(Fe) Structure with a Zeolitic Architecture of the MTN Type Chem 2017 3, 303-322DOI: (10.1016/j.chempr.2017.06.007) Copyright © 2017 Elsevier Inc. Terms and Conditions