Shehzahdi S. Moonshi, 1,2 Cheng Zhang,1,2 Simon Puttick,1,2 Stephen Rose,3 Nicholas Fisk,4 Kishore Bhakoo,5 Brett Stringer,6 Andrew K. Whittaker1,2*

 

1Australian Institute for Bioengineering and Nanotechnology, The University of Queensland,   Brisbane QLD, 4072, 2ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, 3UQ Health Science Building, Royal Brisbane and Women's Hospital, Herston, QLD, 4029, 4UQ Centre for Clinical Research, The University of Queensland, Herston, QLD, 4029, 5Singapore Bioimaging Consortium (A*STAR), Helios, 02-02, Singapore, 138667 6Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, Herston, QLD, 4029

 

There is currently intense interest in new methods for understanding the fate of therapeutically relevant cells, such as mesenchymal stem cells (MSCs). The absence of a confounding background signal makes 19F MRI one of the most attractive modalities for the tracking of injected cells in vivo. We describe here the synthesis of novel partly-fluorinated polymeric nanoparticles (poly(OEGMA-co-PFPE)) with a high fluorine content of 21.4 wt %  and small size of 12 nm, using perfluoropolyether (PFPE) methacrylate as the fluorine monomer and oligo(ethylene glycol) methacrylate (OEGMA) as the hydrophilic moiety via reversible addition−fragmentation chain transfer (RAFT) polymerisation. MSCs derived from human placenta (PMSCs) were labelled successfully with the copolymers ex vivo without the need for electroporation or transfection agents. The copolymers have favorable cell uptake profiles and excellent MRI performance. To facilitate cell studies, the polymer was further conjugated with a fluorescent dye creating a dual-modal imaging agent. The efficacy of labeling of MSCs was assessed using 19F NMR, flow cytometry and confocal microscopy. The labeling efficiency of 2.6 ± 0.1 x 101219F atoms per cell, and viability of >90 % demonstrates good tolerance by the cells. This loading translates to a minimum 19F MRI detection sensitivity of ~ 7.4 x 103 cells/voxel. Importantly, preliminary in vivo data demonstrates that labeled cells can be readily detected within a short acquisition scan period (12 minutes). Additionally, these copolymers have no effect on typical MSCs characteristics. Hence, these copolymers show outstanding potential for 19F MRI cellular tracking and for quantification of non-phagocytic and therapeutically relevant cells in vivo.

Biographic Details

Shehzahdi Shebbrin Moonshi

PhD student, Australian Institute for Bioengineering

and Nanotechnology, Australia.

E-mail: shehzahdi.moonshi@uq.net.au

Research interests: Biomaterials, stem cells, MRI