In Vivo Evaluation of Magnetic Targeting in Mice Colon Tumors with Ultra-Magnetic Liposomes Monitored by MRI
The development of theranostic nanocarriers as an innovative therapy against cancer has been improved by targeting properties in order to optimize the drug delivery to safely achieve its desired therapeutic effect. The aim of this paper is to evaluate the magnetic targeting (MT) efficiency of ultra-magnetic liposomes (UML) into CT26 murine colon tumor by magnetic resonance imaging (MRI).
Dynamic susceptibility contrast MRI was applied to assess the bloodstream circulation time. A novel semi-quantitative method called %I0.25, based on the intensity distribution in T2*-weighted MRI images was developed to compare the accumulation of T2 contrast agent in tumors with or without MT. To evaluate the efficiency of magnetic targeting, the percentage of pixels under the intensity value I0.25 (I0.25 = 0.25(Imax − Imin)) was calculated on the intensity distribution histogram.
This innovative method of processing MRI images showed the MT efficiency by a %I0.25 that was significantly higher in tumors using MT compared to passive accumulation, from 15.3 to 28.6 %. This methodology was validated by ex vivo methods with an iron concentration that is 3-fold higher in tumors using MT.
We have developed a method that allows a semi-quantitative evaluation of targeting efficiency in tumors, which could be applied to different T2 contrast agents.
Key wordsMRI Magnetic targeting Magnetic nanoparticle Liposome Image analysis method Tumor
This work was supported by the LabEx MiChem part of French state funds managed by the ANR within Le Programme Investissements d’Avenir under reference ANR-11-IDEX-0004-02. In vivo imaging was performed at the Life Imaging Facility of Paris Descartes University (LIOPA from the Plateform Imageries du Vivant – PIV) and partly supported by CNRS and ENSCP, ANR LightLab program.
We are grateful to Institut Français Weizmann for a postdoctoral grant (GR), Emmanuel Aubry from ALIPP6 for ICP analysis, Claire Wilhelm for magnetophoresis experiments, Cellular Imaging facility Imagic of Institut Cochin for confocal microscopy, and to Jean-Michel Guigner for CryoTEM.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 7.Mikhaylov G, Mikac U, Magaeva AA, Itin VI, Naiden EP, Psakhye I, Babes L, Reinheckel T, Peters C, Zeiser R, Bogyo M, Turk V, Psakhye SG, Turk B, Vasiljeva O (2011) Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment. Nat Nano Technol 6:594–602CrossRefGoogle Scholar
- 22.Lorenzato C, Oerlemans C, van Elk M, Geerts WJC, Denis de Senneville B, Moonen C, Bos C (2016) MRI monitoring of nanocarrier accumulation and release using gadolinium-SPIO co-labelled thermosensitive liposomes: Gd-TSM for nanocarrier localization and monitoring of release using MRI. Contrast Media Mol Imaging 11:184–194CrossRefGoogle Scholar
- 25.Malinge J, Géraudie B, Savel P, Nataf V, Prignon A, Provost C, Zhang Y, Ou P, Kerrou K, Talbot JN, Siaugue JM, Sollogoub M, Ménager C (2017) Liposomes for PET and MR imaging and for dual targeting (magnetic field/glucose moiety): synthesis, properties, and in vivo studies. Mol Pharm 14:406–414CrossRefGoogle Scholar
- 31.Haacke EM, Brown RW, Thompson MR, et al. (2014) Magnetic properties of tissues: theory and measurement. In: Magnetic resonance imaging: Physical Principles and Sequence Design. Ed. John Wiley & Sons. New York: Wiley-Liss, pp 741–779Google Scholar
- 34.Melemenidis S, Jefferson A, Ruparelia N, Akhtar AM, Xie J, Allen D, Hamilton A, Larkin JR, Perez-Balderas F, Smart SC, Muschel RJ, Chen X, Sibson NR, Choudhury RP (2015) Molecular magnetic resonance imaging of angiogenesis in vivo using polyvalent cyclic RGD-Iron oxide microparticle conjugates. Theranostics 5:515–529CrossRefGoogle Scholar