Ferri-liposomes as an mri-visible drug-delivery system for targeting tumours and their microenvironment

ABSTRACT The tumour microenvironment regulates tumour progression and the spread of cancer in the body. Targeting the stromal cells that surround cancer cells could, therefore, improve the

effectiveness of existing cancer treatments. Here, we show that magnetic nanoparticle clusters encapsulated inside a liposome can, under the influence of an external magnet, target both the

tumour and its microenvironment. We use the outstanding _T_2 contrast properties (_r_2 = 573–1,286 s−1 mM−1) of these ferri-liposomes, which are ∼95 nm in diameter, to non-invasively monitor

drug delivery _in vivo_. We also visualize the targeting of the tumour microenvironment by the drug-loaded ferri-liposomes and the uptake of a model probe by cells. Furthermore, we used the

ferri-liposomes to deliver a cathepsin protease inhibitor to a mammary tumour and its microenvironment in a mouse, which substantially reduced the size of the tumour compared with systemic

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our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS THE ROLE OF TUMOR MODEL IN MAGNETIC TARGETING OF MAGNETOSOMES AND ULTRAMAGNETIC LIPOSOMES Article Open access 08

February 2023 CURRENT ADVANCES IN THE USE OF EXOSOMES, LIPOSOMES, AND BIOENGINEERED HYBRID NANOVESICLES IN CANCER DETECTION AND THERAPY Article 04 April 2022 IMAGING-GUIDED PRECISION

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The authors thank Yu.F. Ivanov (Tomsk Scientific Center) for transmission electron microscopy, G. Kapun (National Institute of Chemistry) for scanning electron microscopy, M. Škarabot (Jozef

Stefan Institute) for atomic force microscopy, J. Ščančar and M. Vahčič (Jozef Stefan Institute) for flame atomic absorption spectrometry, I.V. Sukhodolo, R.I. Pleshko, A.N. Dzuman, I.V.

Milto and L.M. Ogorodova (Siberian State Medical University) for help in the acute toxicity study, and A. Sepe, M. Butinar, M. Trstenjak-Prebanda and A. Petelin (Jozef Stefan Institute),

O.G. Terekhova (Tomsk Scientific Center), M. Tacke and N. Klemm (Institut für Molekulare Medizin und Zellforschung) for technical and methodological assistance, G. Salvesen (Sanford-Burnham

Medical Research Institute) for valuable discussions, and R.H. Pain (Jozef Stefan Institute) for critical reading of the manuscript. JPM-565 was kindly provided by the Drug Synthesis and

Chemistry Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute. The research leading to these results was supported in part by

the European Community's Seventh Framework Programme FP7/2007-2011 (grant agreement no. 201279, Microenvimet, O.V., T.R., C.P. and B.T.), the Slovenian Research Agency (research grant

no. P1-0140, B.T.), the Russian Foundation for Basic Research (project no. 07-04-12170, E.P.N.), the United States Civilian Research and Development Foundation (project no. Y4-C16-05, A.A.M

and V.I.I.) and the DFG SFB 850 (to T.R., C.P. and R.Z.). AUTHOR INFORMATION Author notes * Ivan Psakhye Present address: Present address: Department of Molecular Cell Biology, Max Planck

Institute of Biochemistry, Martinsried 82152, Germany, AUTHORS AND AFFILIATIONS * Department of Biochemistry and Molecular and Structural Biology, Jozef Stefan Institute, Ljubljana, SI-1000,

Slovenia Georgy Mikhaylov, Ivan Psakhye, Vito Turk, Boris Turk & Olga Vasiljeva * Department of Condensed Matter Physics, Jozef Stefan Institute, Ljubljana, SI-1000, Slovenia Ursa Mikac

* Centre of Excellence EN-FIST, Ljubljana, SI-1000, Slovenia Ursa Mikac * Tomsk Scientific Center, Siberian Branch of Russian Academy of Sciences, Tomsk, 634055, Russia Anna A. Magaeva, 

Volya I. Itin, Evgeniy P. Naiden & Sergey G. Psakhye * Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg, Freiburg, 79104, Germany Liane Babes, 

Thomas Reinheckel & Christoph Peters * BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universität Freiburg, Freiburg, 79104, Germany Thomas Reinheckel & Christoph

Peters * Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, 79106, Germany Robert Zeiser * Department of Pathology, Microbiology and Immunology, Stanford

University School of Medicine, California, 94305, USA Matthew Bogyo * Center of Excellence CIPKEBIP, Ljubljana, SI-1000, Slovenia Vito Turk & Boris Turk * Institute of Strength Physics

and Materials Science, Tomsk, 634021, Russia Sergey G. Psakhye * Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, SI-1000, Slovenia Boris Turk * Center of

Excellence Nanosciences and Nanotechnology, Ljubljana, SI-1000, Slovenia Boris Turk Authors * Georgy Mikhaylov View author publications You can also search for this author inPubMed Google

Scholar * Ursa Mikac View author publications You can also search for this author inPubMed Google Scholar * Anna A. Magaeva View author publications You can also search for this author

inPubMed Google Scholar * Volya I. Itin View author publications You can also search for this author inPubMed Google Scholar * Evgeniy P. Naiden View author publications You can also search

for this author inPubMed Google Scholar * Ivan Psakhye View author publications You can also search for this author inPubMed Google Scholar * Liane Babes View author publications You can

also search for this author inPubMed Google Scholar * Thomas Reinheckel View author publications You can also search for this author inPubMed Google Scholar * Christoph Peters View author

publications You can also search for this author inPubMed Google Scholar * Robert Zeiser View author publications You can also search for this author inPubMed Google Scholar * Matthew Bogyo

View author publications You can also search for this author inPubMed Google Scholar * Vito Turk View author publications You can also search for this author inPubMed Google Scholar * Sergey

G. Psakhye View author publications You can also search for this author inPubMed Google Scholar * Boris Turk View author publications You can also search for this author inPubMed Google

Scholar * Olga Vasiljeva View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS G.M., U.M., I.P., S.G.P., B.T. and O.V. conceived and designed the

experiments. G.M., U.M., L.B. and O.V. performed the experiments. G.M., U.M., S.G.P., B.T. and O.V. analysed the data. T.R., C.P. and R.Z. contributed transgenic mouse models and animal

imaging. M.B. contributed JPM-565 inhibitor. A.A.M., V.I.I., E.P.N. and S.G.P. supplied the magnetic nanoparticles. S.G.P., V.T., B.T. and O.V. supervised the project. G.M., S.G.P., B.T. and

O.V. wrote the manuscript. All authors discussed the results and commented on the manuscript. CORRESPONDING AUTHORS Correspondence to Boris Turk or Olga Vasiljeva. ETHICS DECLARATIONS

COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION Supplementary information (PDF 3236 kb) RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Mikhaylov, G., Mikac, U., Magaeva, A. _et al._ Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and

their microenvironment. _Nature Nanotech_ 6, 594–602 (2011). https://doi.org/10.1038/nnano.2011.112 Download citation * Received: 31 January 2011 * Accepted: 16 June 2011 * Published: 07

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