# Bimodal nanoparticles for MRI and optical imaging based on polymer vesicles (polymersomes) for image-guided drug delivery

Marie Devreux, Céline Henoumont, Fabienne Dioury, Sébastien Boutry, Angela Mutschler, Chloé Lassalle, Olivier Vacher, Sébastien Moins, Olivier Coulembier, Luce Vander Elst, et al.

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To cite this version:

Marie Devreux, Céline Henoumont, Fabienne Dioury, Sébastien Boutry, Angela Mutschler, et al. Bimodal nanoparticles for MRI and optical imaging based on polymer vesicles (polymersomes) for image-guided drug delivery. 7th Annual Meeting SFNano (SFNano 2021), Dec 2021, Angers, France. . hal-04056861

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# Bimodal nanoparticles for MRI and optical imaging based on polymer vesicles (polymersomes) for image-guided drug delivery

Devreux Marie [a,d], Henoumont Céline [a], Dioury Fabienne [b], Boutry Sébastien [c], Mutschler Angela [d], Lassalle Chloé [d], Vacher Olivier [b], Moins Sébastien [e], Coulembier Olivier [e], Vander Elst Luce [a], Port Marc [b], Muller Robert [a] [c], Sandre Olivier [d] and Laurent Sophie [a] [c]

[a] University of Mons, UMONS, General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, 19 Avenue Maistriau, 7000 Mons (Belgium)

[b] Conservatoire national des arts et métiers, CMGPCE Laboratory, EA 7341, Paris (France)

[c] Center for microscopy and molecular imaging (CMMI), 8 rue Adrienne Bolland, 6041 Charleroi (Belgium)

[d] University of Bordeaux, CNRS, Bordeaux-INP ENSCBP, Laboratory of Organic Polymer Chemistry, 16 Avenue Pey-Berland, 33607 Pessac (France)

[e] University of Mons (UMONS), Laboratory of Polymeric and Composites Materials, 20 Place du Parc, 7000 Mons (Belgium)

LCPO
Laboratoire de Chimie
des Polymères Organiques

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## 1. Introduction

In modern medicine, bioimaging acquired a leading place in the diagnosis setting. This is why researches are continually carrying out to improve the available techniques. One of the most used techniques to obtain anatomical information is magnetic resonance imaging (MRI). Although it is a highly resolutive technique, it has low sensitivity, which needs to be enhanced by a contrast agent. However, the commercially available contrast agents are based on gadolinium complexes, which can lead to nephrogenic systemic fibrosis. That is why the synthesis of new complexes based on another magnetic cation, such as manganese (Mn²⁺), is interesting. Manganese ions are indeed potentially less toxic since they are naturally present in the body. This study shows the interest of pylcen derivatives complexed with Mn²⁺ ions. Further improvement will consist in the relaxometric study of the macrocyclic complexes grafted on polymer nano-vesicles, also called “polymersomes”, made of a pH-sensitive polyester shell encapsulating doxorubicin and ZW800-1 in order to obtain a controlled release of the drug in the acidic tumoral environment which could be monitored by MRI and optical imaging.

## 2. Pylcen based manganese complexes

### Phantom images

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<table><thead><tr><th></th><th>MnL<sub>1</sub>H</th><th>MnL<sub>2</sub>COO<sup>-</sup></th><th>MnL<sub>3</sub>CH</th><th>MnL<sub>4</sub>NH<sub>3</sub><sup>+</sup></th><th>Gd-DOTA<sup>1</sup></th></tr></thead><tbody><tr><td>r<sub>1</sub> (s<sup>-1</sup>·mM<sup>-1</sup>)</td><td>2.8 ± 0.1</td><td>2.7 ± 0.1</td><td>3.1 ± 0.1</td><td>2.95 ± 0.1</td><td>3.2 ± 0.1</td></tr><tr><td>9.4T, 37°C</td><td></td><td></td><td></td><td></td><td></td></tr></tbody></table>

### In progress

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$$MnL_{1}H \quad R = H$$

$$MnL_{2}COO^{-} \quad R = OCH_{2}COO^{-}$$

$$MnL_{3}CH \quad R = OCH_{2}CONHCH_{2}CCH$$

$$MnL_{4}NH_{3}^{+} \quad R = OCH_{2}CONH(CH_{2})_{2}NH_{3}^{+}$$

<figure><img src="image_7.png" /><figcaption>Gd-DOTA</figcaption></figure>

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## 3. Polymersomes vesicles

### Nanoprecipitation of copolymers to prepare polymersomes

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### Cumulative release assay by automated dissolution apparatus (SOTAX® USP-4)³:

Doxorubicin release curves were detected from UV-Vis absorbance at 483 nm in flow-through conditions at 37°C and at two pH : in acidic medium (pH 5.5) to mimic tumoral micro-environment and at physiological medium (pH 7.4). Compared to control, a burst of drug release is observed within the 1st two hours instead of the ZW800-1 that show no release at 769 nm.

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## 4. Conclusions and perspectives

This study shows that these four manganese-pylcen derivatives are promising T₁ MRI contrast agents to palliate adverse effects of gadolinium complexes. Moreover, different functions can be conjugated to obtain a functionalized pylcen that can be grafted onto the polymersomes surface to improve relaxivity and bring pH-sensitivity to the MR signal. The release of doxorubicin is currently being optimized to afford a more sustained drug release under acidic conditions in addition to the observed burst at the beginning of the test.

## 5. Acknowledgements

This work was performed with financial support of SIRIC BRIO (COMMUCAN project), FNRS, ARC, the Walloon Region (Gadolymph, Holocancer and Interreg projects), and the COST actions TD1004, TD1007, TD1402, and CM1006. Authors thank the Center for Microscopy and Molecular Imaging (CMMI), and the bioprofiling platform supported by European Regional Development Fund and Wallonia).

université
de BORDEAUX

UMONS
Université de Mons

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2. A. Hannecart, D. Stanicki, L. Vander Elst, R. N. Muller, O. Sandre, C. Schatz, S. Lecommandoux, A. Brûlet, S. Laurent, *J Mater Chem* B 2019, 7, 4692–4705

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4. All sketches were designed with Biorender® and Blender®