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02 Nanoparticles for Simultaneous Cell Tracking & Microrna Delivery
  1. RSM Gomes1,2,3,4,
  2. R Neves1,2,
  3. LE Cochlin4,
  4. AF Lima1,2,
  5. R Carvalho2,
  6. P Korpisalo5,
  7. G Dragneva5,
  8. A Paiva2,
  9. S Ylä-Herttuala5,
  10. K Clarke4,
  11. CA Carr4,
  12. L Ferreira1,2
  1. 1Biomaterials & Stem Cells Based Therapeutics Lab, Biocant, Cantanhede, Portugal
  2. 2Centre of Neurosciences and Cell Biology, University of Coimbra, Portugal
  3. 3Cardiovascular Biology & Medicine, Rayne institute, University College London, UK
  4. 4Cardiac Metabolism Research Group, Department of Physiology, Anatomy & Genetics, Oxford University, UK
  5. 5Gene Therapy & Angiogenesis group, University of Eastern Finland, Finland

Abstract

Magnetic resonance imaging (MRI) is a powerful non-invasive imaging platform which, in combination with contrast agents, can be used to track stem cell fate after transplantation. Here, we developed a novel formulation of nanoparticles (NPs), based on poly(lactic-co-glycolic acid) (PLGA) which is a biocompatible polymer approved for human use. PLGA NPs are bioluminescent and contain fluorine, enabling cell tracking using optical imaging or 19F MRI, and can be used as vectors for microRNA (miR) delivery.

The PLGA NPs (average diameter 170nm, positive (7.0±1.7 mV) zeta potential) successfully labelled HUVECs (63.18±0.96%) and mononuclear cells (MNCs; 80.75±1.21%) with only 10% of cells dying after 24 h of NP exposure. Labelled MNCs, administered to the infarcted rat heart, could be detected in vivo using 19F MRI.

HUVECs were incubated with miRNA-complexed NPs to deliver pro-survival and pro-angiogenic miRs (miR-132, miR-424 and antagomir-92a (amiR-92a)) and cultured on matrigel to assess their capacity to form vascular networks. Cells transfected with miR-132 NPs and miR-424 NPs yielded vascular networks with greater tube length and more branching points than those transfected with amiR-92a NPs. Furthermore, NPs were more efficient at transfection than the commercially available reagent, SIPORT.

Endothelial cells labelled with miR-132 NPs were administered to rodent models of hind limb ischemia. Labelled cells could be tracked in vivo using 19F MRI, improved cell survival and induced neo-angiogenesis (measured using ultrasound and histology).

This work shows for the first time a NP formulation that can be used both to track cells and successfully deliver miRs.

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