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Ru(ii)/BODIPY core co-encapsulated ratiometric nanotools for intracellular O2 sensing in live cancer cells

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posted on 22.10.2021, 14:46 by Karmel Sofia Gkika, Anna Kargaard, Christopher S Burke, Ciaran Dolan, Andreas HeiseAndreas Heise

Oxygen is a crucial reagent in many biochemical processes within living cells and its concentration can be an effective marker in disease, particularly in cancer where tissue hypoxia has been shown to indicate tumour growth. Probes that can reflect the oxygen concentration and distribution using ratiometric signals can be applied to a range of conventional methods without the need for specialised equipment and are particularly useful. The preparation and in cellulo study of luminescent ratiometric core–shell nanoparticles are presented. Here, a new lipophilic and oxygen-responsive Ru(II) tris-heteroleptic polypyridyl complex is co-encapsulated with a reference BODIPY dye into the core of poly-L-lysine-coated polystyrene particles. The co-core encapsulation ensures oxygen response but reduces the impact of the environment on both probes. Single wavelength excitation of the particles, suspended in aqueous buffer, at 480 nm, triggers well-resolved dual emission from both dyes with peak maxima at515 nm and 618 nm. A robust ratiometric oxygen response is observed from water, with a linear dynamic range of 3.6–262μM which matches well with typical biological ranges. The uptake of RuBDP NPs was found to be cell-line dependent, but in cancerous cell lines, the particles were strongly permeable with late endosomal and partial lysosomal co-staining observed within 3 to 4 hours, eventually leading to extensive staining of the cytoplasm. The co-localisation of the ruthenium and BODIPY emission confirms that the particles remain intact in cellulo with no indication of dye leaching. The ratiometric O2sensing response of the particles in cellulo was demonstrated using a plate-based assay and by confocal xyλ scanning of cells exposed to hypoxic conditions

Funding

Irish Research Council Scholarship: IRC Government of Ireland Postgraduate Scholarship GOIPG/2016/702

Government of Ireland Postdoctoral Fellowship, GOIPD/2018/495.

Science Foundation Ireland under grant numbers 19/FFP/6428 and 12/RC/2276_P2

Science Foundation Ireland(SFI) and the European Regional Development Fund (ERDF)under grant number 13/RC/2073.

History

Comments

The original article is available at https://pubs.rsc.org/

Published Citation

Gkika KS, Kargaard A, Burke CS, Dolan C, Heise A, Keyes TE. Ru(ii)/BODIPY core co-encapsulated ratiometric nanotools for intracellular O2 sensing in live cancer cells. RSC Chemical Biology. 2021;2(5):1520-33.

Publication Date

28 July 2021

Department/Unit

  • Chemistry
  • CURAM Centre for Research in Medical Devices
  • Amber (Advanced Material & Bioengineering Research) Centre

Research Area

  • Biomaterials and Regenerative Medicine
  • Chemistry and Pharmaceutical Sciences

Publisher

Royal Society of Chemistry (RSC)

Version

  • Published Version (Version of Record)