Imparting Functionality to MOF Nanoparticles by External Surface Selective Covalent Attachment of Polymers

Selective functionalization of the external surface of porous nanoparticles is of great interest for numerous potential applications in the field of nanotechnology. Regarding metal–organic frameworks (MOFs), few methods for such modifications have been reported in the literature. Herein, we focus on the covalent attachment of functional polymers on the external surface of MIL-100­(Fe) nanoparticles in order to implement properties such as increased chemical and colloidal stability or dye-labeling for the investigation of the particles by fluorescence based techniques. We prove covalent nanoparticles-polymer bond formation by liquid NMR after dissolution of the functionalized MOF under mild conditions and estimate the amount of covalently attached polymer by UV–vis spectroscopy. The functionalization of the MOF nanoparticles with fluorescently labeled polymers enables the investigation of nanoparticle uptake into tumor cells by fluorescence microscopy. Furthermore, the influence of the polymer shell on the magnetic resonance imaging activity of MIL-100­(Fe) is investigated in detail. The functionalization approach presented here is expected to enable the fabrication of hybrid nanomaterials, extending the enormous chemical space of MOFs into polymer materials

Column charts of SI_10min in the therapy and control group at follow-up.

<p>Note the significant difference (p < 0.05) between the mean values of SI_10min between the therapy and the control group at the follow-up.</p

Individual immunohistochemical values.

<p>Individual immunohistochemical values.</p

Line regression analysis for the correlation between CEUS parameter of VEGFR2-specific binding and immunohistochemical VEGFR2 expression.

<p>Note the significant correlation between the values of SI_8min and the number of VEGFR2 positive stained vessels (Spearman´s ρ = 0.66, p = 0.003) for the therapy and the control group.</p

Individual DCE-MRI values.

<p>Individual DCE-MRI values.</p

Representative CEUS images of a rat with a subcutaneous tumor xenograft (white arrows) under treatment.

<p>Therapy group (red) and control group (blue) at baseline and follow-up. Left side: early vascular phase with BR55 as a functional imaging biomarker; right side: late phase of VEGFR2-specific binding with BR55 as a molecular imaging biomarker 8 minutes after contrast injection. Note the significant lower number of circulating microbubbles in the early vascular phase as well as the significant lower number of bound microbubbles in the late phase at follow-up in the therapy group, compared to baseline and compared to the control group.</p

Individual molecular CEUS values.

<p>Individual molecular CEUS values.</p

Correlations between functional CEUS values and immunohistochemistry.

<p>Correlations between functional CEUS values and immunohistochemistry.</p

Individual values of functional parameters of tumor microcirculation in the therapy group at baseline and follow-up.

<p>Note: F_p: plasma flow [mL/100 mL/min]; V_p: plasma volume [%]; PS: permeability-area surface product [mL/100 mL/min]; ^abaseline; ^bfollow-up.</p

Correlations between molecular CEUS values and immunohistochemistry.

<p>Correlations between molecular CEUS values and immunohistochemistry.</p