Thematic Session: Nanochemistry & Nanoparticles / Nanobiosciences & Nanomedecine / ANR
Disciplinary fields involved: Polymer Chemistry, Physical Chemistry, Biological Applications
Keywords (max. 4-5): Polymers, Anisotropic Nanoparticles, Irradiation, Magnetism, Cell Death

Magnetic Polymersome Deformation by a Static Magnetic Field

Diana Kazaryan¹, Sabrina Lacomme², Etienne Gontier², Loubna Kehal³, Véronique Gigoux³, Marin Tadić⁴, Ana Mraković⁴, Sisareuth Tan⁵, Olivier Lambert⁵, Frédéric Peruch,¹ and Olivier Sandre¹

1. Laboratory of Organic Polymer Chemistry (LCPO), Univ. of Bordeaux, CNRS, Bordeaux INP, Pessac, France

2. Bordeaux Imaging Center (BIC), CNRS / INSERM / Univ. of Bordeaux, Bordeaux, France

3. Toulouse Research Center on Cancerology (CRCT), INSERM / CNRS / Univ. Paul Sabatier, Toulouse, France

4. VINCA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, Univ. of Belgrade, Vinca, Serbia

5. Chemical Biology of Membranes & Nano-objects (CBMN), CNRS, Univ/INP Bordeaux, Pessac, France

Incorporation of superparamagnetic iron oxide nanoparticles (SPION) in polymer vesicles has been mostly studied as means to cancer cell death induction via drug encapsulation and delivery at the tumor site [1]. Nonspherical polymeric nanostructures prevail over spherical ones in terms of circulation time, cell uptake amount and kinetics [2]. Our study aims at preparing such anisotropic magnetic polymersomes and use them as mechanical actuators to destroy cells by mechanical torques under rotating magnetic fields. Such "nano-blenders" were prepared by co-assembly of hydrophobically SPIONs with amphiphilic block copolymers (BCPs) constituting the membranes. Two topologies of BCPs were designed: triblock BCPs with either linear or comb-like topology. While the hydrophilic block was always poly(ethylene oxide) (PEO), the hydrophobic part was composed of two polymers chosen for their soft rubbery state (i.e. low Tg), polyisoprene (PI) which double-bonds were epoxidized and further cross-linked, and poly(trimethylene carbonate) (PTMC), both ones being reported to self-assemble into polymersomes when designed as diblock copolymer with PEO. Then we studied the deformation of those vesicles in a static magnetic field and the shift of their morphology from spherical to (slightly) elongated. During this elongation process, the hydrophobic membranes were crosslinked by irradiation with either UV or Γ rays. For this aim, a fraction of double bonds in the PI block was epoxidized followed by cationic ring opening via a cationic photo-initiator. These vesicles were incorporated into cancer cells, and owing to their anisotropy used to exert mechanical torques when rotating magnetic field was applied, forcing the vesicles to rotate, thereby damaging internal cell compartments, and leading to apoptosis.

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**References (max. 5):**

1. H. Oliveira, E. Pérez-Andrés, J. Thevenot, O. Sandre, E. Berra, and S. Lecommandoux, "Magnetic field triggered drug release from polymersomes for cancer therapeutics," J. Control. Release 169, 165–170 (2013).

2. E. Scarpa, C De Pace, AS Joseph, SC de Souza, A Poma E Liatsi-Douvitsa, C Contini, V De Matteis, J Samitier Martí, G. Battaglia, L. Rizzello, "Tuning cell behavior with nanoparticle shape", PLoS One 15, e0240197E (2020).

**Acknowledgement:**

This work received funding from the French National Research Agency, project "Magnetic VESicle Rotation Induced Cell Killing" (MAVERICK, ANR-19-CE09-0024) and from the French Ministry of Foreign Affairs (PHC Pavlic Savić 2023 "Preservation of magnetic polymersomes' anisotropic morphology *via* gamma irradiation induced crosslinking")