Poster Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Enhancing Anticancer Strategies through Metal Coordination via Terpyridine-Functionalized Polysaccharide Nanoparticles (#443)

Roberta R Panebianco 1 , Robert R Cavanagh 2 , Enrico E Falcone 3 , Eleni E Axioti 3 , Ruman R Rahman 4 , Luisa L Ciano 3 , Vincenzo V Taresco 3 , Graziella G Vecchio 1
  1. University of Catania, Catania, ITALY, Italy
  2. Children’s Brain Tumour Research Centre, Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham, UK
  3. School of Chemistry, University of Nottigham, Nottingham, UK
  4. School of Pharmacy, University of Nottingham, Nottingham, UK

Cyclodextrins (CDs) are versatile building blocks for developing therapeutic platforms.[1] We devised CD-based nanoparticles (NPs) incorporating terpyridine (pβCDtpy), a chelator that enables customization through coordination chemistry, by forming metal complexes with terpyridine derivatives.[2] Terpyridine was functionalized with glucose (Glc), galactose (Gal), tocopherol (Toco) or biotin (Bio) to exploit receptor-mediated uptake in cancer cells. Among them, the TpyBio conjugate demonstrated superior activity in glioblastoma cells and was selected to decorate the tpy-based NPs.

A cross-linked β-CD polymer was functionalized with 3-([2,2’:6’,2’’-terpyridin]-4’-yloxy)propan-1-amine (TpyNH2) via condensation reaction as well as the TpyBio[3] and TpyToco conjugates. The TpyGlc[4] and TpyGal derivatives were synthesized by nucleophilic substitution reactions. Cu2+ and Fe2+ complexes with pβCDtpy (pβCDtpy-M2+ or pβCDtpy-M2+-TpyBio) were prepared by mixing a metal ion solution with the ligands and characterized by UV-Vis spectroscopy. The in vitro experiments were conducted in glioblastoma (GIN28) cells.

The functionalization of pβCD was confirmed by NMR spectroscopy, showing the presence of 48 tpy units. The complexation properties of the tpy-based NPs were studied by spectrophotometric titration, with Fe2+ or Cu2+ salt solutions. The diagnostic band at 313 nm was observed, ascribed to the conformational change from the trans/trans to cis/cis conformation change of tpy. Also, upon the stepwise addition of Fe2+ a band at 558 nm arises, due to the metal-ligand charge transfer (MLCT) transition.[5] The antiproliferative properties were assessed in GIN28 cells. All the compounds exhibited IC50 values lower than those of Temozolomide (TMZ, IC50 = 214.15 µM), a commonly used drug for treating glioblastoma. The most promising system was the ternary complex in the presence of copper (pβCDtpy-Cu2+-TpyBio), whose IC50 was about 0.33 ±0.09 µM.

This study presents a promising CD-based nanoparticle platform functionalized with terpyridine derivatives for targeted cancer therapy. The incorporation of metal ions, particularly Cu2+, into terpyridine-functionalized nanoparticles (NPs) amplified their therapeutic impact, exhibiting significant cytotoxicity against glioblastoma cells.

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  2. [2] R. Abhijnakrishna, K. Magesh, A. Ayushi, S. Velmathi, Coordination Chemistry Reviews 2023, 496, 215380.
  3. [3] R. Panebianco, M. Viale, N. Bertola, F. Bellia, G. Vecchio, Dalton Transactions 2022, 51, 5000–5003.
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