Red‐light activation of a microtubule polymerization inhibitor via amide functionalization of the ruthenium photocage

Metals in Catalysis, Biomimetics & Inorganic Material

Multitarget thiol-activated tetrapyridyl gold(III) complexes for hypoxic cancer therapy

Metals in Catalysis, Biomimetics & Inorganic MaterialsPharmacologyMedicinal Chemistr

In vitro nephrotoxicity and anticancer potency of newly synthesized cadmium complexes

Complexes based on heavy metals have great potential for the treatment of a wide variety of cancers but their use is often limited due to toxic side effects. Here we describe the synthesis of two new cadmium complexes using N(4)-phenyl-2-formylpyridine thiosemicarbazone (L1) and 5-aminotetrazole (L2) as organic ligands and the evaluation of their anti-cancer and nephrotoxic potential in vitro. The complexes were characterized by Single-crystal X-ray data diffraction, 1HNMR, FT-IR, LC/MS spectrometry and CHN elemental analysis. Next, cytotoxicity of these cadmium complexes was evaluated in several cancer cell lines, including MCF-7 (breast), Caco-2 (colorectal) and cisplatin-resistant A549 (lung) cancer cell lines, as well as in conditionally-immortalized renal proximal tubule epithelial cell lines for evaluating nephrotoxicity compared to cisplatin. We found that both compounds were toxic to the cancer cell lines in a cell-cycle dependent manner and induced caspase-mediated apoptosis and caspase-independent cell death. Nephrotoxicity of these compounds was compared to cisplatin, a known nephrotoxic drug, in vitro. Our results demonstrate that compound {2}, but not compound {1}, exerts increased cytotoxicity in MCF-7 and A549 cell lines, combined with reduced nephrotoxic potential compared to cisplatin. Together these data make compound {2} a likely candidate for further development in cancer treatment

In vivo metallophilic self-assembly of a light-activated anticancer drug

Self-assembling molecular drugs combine the easy preparation typical of small-molecule chemotherapy and the tumour-targeting properties of drug-nanoparticle conjugates. However, they require a supramolecular interaction that survives the complex environment of a living animal. Here we report that the metallophilic interaction between cyclometalated palladium complexes generates supramolecular nanostructures in living mice that have a long circulation time (over 12 h) and efficient tumour accumulation rate (up to 10.2% of the injected dose per gram) in a skin melanoma tumour model. Green light activation leads to efficient tumour destruction due to the type I photodynamic effect generated by the self-assembled palladium complexes, as demonstrated in vitro by an up to 96-fold cytotoxicity increase upon irradiation. This work demonstrates that metallophilic interactions are well suited to generating stable supramolecular nanotherapeutics in vivo with exceptional tumour-targeting properties