Highly luminescent metallacages featuring bispyridyl ligands functionalised with BODIPY for imaging in cancer cells

Abstract

Recently, 3-dimensional supramolecular coordination complexes of the metallacage type have been shown to hold promise as drug delivery systems for different cytotoxic agents, including the anticancer drug cisplatin. However, so far only limited information is available on their uptake and sub-cellular localisation in cancer cells. With the aim of understanding the fate of metallacages in cells by fluorescence microscopy, three fluorescent Pd2L4 metallacages were designed and synthesised by self-assembly of two types of bispyridyl ligands (L), exo-functionalised with boron dipyrromethene (BODIPY) moieties, with Pd(II) ions. The cages show high quantum yields and are moderately stable in the presence of physiologically relevant concentration of glutathione. Furthermore, the cages are able to encapsulate the anticancer drug cisplatin, as demonstrated by NMR spectroscopy. Preliminary cytotoxicity studies in a small panel of human cancer cells showed that the metallacages are scarcely toxic in vitro. The marked fluorescence due to BODIPY allowed us to visualise the 2 cages' uptake and sub-cellular localisation inside melanoma cells using fluorescence microscopy, highlighting uptake via active transport mechanisms and accumulation in cytoplasmic vesicles.

Cavity-based applications of metallo-supramolecular coordination cages (MSCCs)

“…The BODIPY-marked cage complexes accumulated in the cytoplasmic vesicles of melanoma cells. 110 Kühn and co-workers attempted the conjugation of tris(bipyridine)ruthenium (a highly luminescent fluorophore) to the Pd 2 L 4 metallacage scaffold via an unsaturated amide or cycloazide linker group to avoid the destruction of the emissive fluorescent group. 111 The resulting cage exhibited a strikingly high quantum yield of 66%, being categorized among the most emissive metallacages.…”

Bioconjugate Supramolecular Pd2+ Metallacages Penetrate the Blood Brain Barrier In Vitro and In Vivo

“…In the future, the cage scaffold could be used to enable imaging in the brain using other modalities (e.g., MRI, PET), not only exploiting noncovalent interactions within its cavity, but also via the exo -functionalization of the pyridyl scaffold with appropriate ligands and linkers . Recently, we explored similar homoleptic [Pd 2 L 4 ] 4+ systems exo -functionalizing of the ligand with fluorescent tags facilitating the study of the cages’ cellular accumulation by fluorescence microscopy in vitro . − Furthermore, the metallacage may enable orthogonal imaging using different techniques (e.g., guest cage designed for PET, host for MRI, etc.). Similarly, the robustness and modular composition of these supramolecular metal-based structures could enable the introduction of tumor targeting moieties (e.g., peptides or antibodies).…”

Light-emitting self-assembled metallacages

“…well-known luminophores are strongly considered for synthesizing light-emitting metallacages [ 32–34 ]. They are often modified with electron-rich recognition motifs and directly used as structural components for metallacages.…”