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Synthesis, photophysical properties and in vitro evaluation of a chlorambucil conjugated ruthenium(II) complex for combined chemo-photodynamic therapy against HeLa cells

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Abstract

The combination of chemotherapy with photodynamic therapy can lead to improved therapeutic efficiencies and reduced side effects compared to conventional chemotherapy. Chlorambucil (CHL) is a DNA alkylating agent, but problems like drug instability, “off-target” binding and in situ monitoring after administration often limit its clinical application. In this regard, we designed a new heteroleptic Ru(II) complex CHL-RuL, bearing a CHL conjugated pendant, which is desired to serve as an image-guided chemo-photodynamic combined theranostic agent. CHL-RuL shows considerable promise as a photosensitizer for two-photon excitation photodynamic therapy: strong and wide UV-Vis absorption bands centered around 400 nm, strong red emission (∼702 nm) with a long lifetime at the microsecond level, moderate singlet oxygen quantum yield, and significant two-photon absorption cross-section (118 GM). More interestingly, this chemical modification affords CHL-RuL greater cellular uptake and remarkable mitochondria accumulation in HeLa cells. Furthermore, CHL-RuL shows a slight selective cytotoxicity toward carcinoma HeLa cells over normal MRC-5 cells. MTT assay results and two-photon scanning cell imaging demonstrate that CHL-RuL exhibits obvious chemo-photodynamic dual action against HeLa cells.

Graphical abstract: Synthesis, photophysical properties and in vitro evaluation of a chlorambucil conjugated ruthenium(ii) complex for combined chemo-photodynamic therapy against HeLa cells

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Publication details

The article was received on 14 Mar 2017, accepted on 08 May 2017 and first published on 08 May 2017


Article type: Paper
DOI: 10.1039/C7TB00702G
Citation: J. Mater. Chem. B, 2017, Advance Article
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    Synthesis, photophysical properties and in vitro evaluation of a chlorambucil conjugated ruthenium(II) complex for combined chemo-photodynamic therapy against HeLa cells

    J. Zhang, M. Pan and C. Su, J. Mater. Chem. B, 2017, Advance Article , DOI: 10.1039/C7TB00702G

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