Journal
JOURNAL OF MATERIALS CHEMISTRY B
Volume 5, Issue 24, Pages 4623-4632Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7tb00702g
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Funding
- Postdoctoral Science Foundation of China [2013M531889]
- NSF of China [21373276]
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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 (similar to 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.
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