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Smart Imaging Probes, Emerging Imaging

Smart multimodal theranostic conjugated polymer nanoparticles for MR/near-IR imaging and photothermal/photodynamic therapy

Project ID: 2019_045

1st supervisor: Mark Green, King’s College London
2nd supervisor: Maya Thanou, King’s College London

Infrared emitting probes are desirable for deep-tissue imaging or real-time surgery, for example wen treating  cancer when tumours can be visualised and removed immediately. They can be used for image guided surgery and/or endoscopic imaging and surgery. There are however, few materials that allow imaging at such wavelengths whilst maintaining emission stability by a prolonged excitation before and through the length of a surgical procedure. We are also interested in adding further imaging modalities – as suggested by surgeons – where we can switch between optical and magnetic resonance (MR) imaging to allow different degrees of tumour identification. For example in the case of colorectal cancer MRI can provide the spatial location in the intestine while a NIRF endoscope can follow and treat these cancers. This present a demanding wish list of probe requirement – IR emission, MR relaxation, stability, and the potential for targeting either by passive (EPR) or active targeting (antibody, affirmer recognition, etc). Nanoparticles allow the simple combination of modalities, and conjugated polymer particles offer unrivalled optical properties, notably brightness and prolonged stability. When combined with iron oxide nanoparticles or Gd-containing lipids, the resulting structure is both optically and MRI active.

IR-emitting polymers are now emerging, with bright emission at notably the first and second biological windows, i.e. between ca. 700 and 1300 nm. We have also found that certain IR-luminescent polymers also generate free radicals and heat upon excitation. By combining iron oxide, the specific polymer and a surface agent that is compatible with biology, we have a stable, biologically-active luminescent/MRI active imaging nanoparticle. By working with collaborators who have experience in surgical applications of multimodal nanoparticles, we will apply the materials to targeting and imaging colorectal cancers in theatre and explore the possibility of a therapeutic outcome using photodynamic therapy (PDT) and photothermal therapy (PTT) at the biological window.

Z-Stack through a HeLa cell after 24 hours of incubation with IR emitting nanoparticles with SPIONs at 1.45 μm steps. Red indicates NPs, whereas blue is DAPI stain. A) Z-stack at maximum intensity, with yellow box indicating area of interest. B) Volume view at maximum intensity, with yellow box indicating area of interest. C) Orthogonal view of z-stack, with slice 10/20 taken as showing NP internalised within the cell. D) Montage of the Z-stack, with 1 indicating bottom of cell to 20 indicating top (depth ~27.8 µm). Scale bar = 20 μm.

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