Encapsulation of a Ru(η6-p-cymene) complex of the antibacterial drug trimethoprim into a polydiacetylene-phospholipid assembly to enhance its in vitro anticancer and antibacterial activities

Abstract

A new organometallic ruthenium(II)–p-cymene complex bearing the antibacterial drug trimethoprim (RATMP(C)) has been synthesised, enwrapped into a polydiacetylene (PDA)-based liposome (Lip-RATMP(C)), and studied for its anticancer and antibacterial activities. The conjugated yne–ene chain of the polymeric backbone of PDA assists the formation of a stable nanoaggregate from which only 50% of the encapsulated complex was leached out even after 110 h under physiological conditions. RATMP(C) shows more efficient DNA cleavage activity than Lip-RATMP(C) and the DNA binding constant of the complex determined using UV-Visible absorption spectral titration illustrates the role of the hydrophobicity and hydrogen bonding propensity of the coordinated ligands in determining the DNA binding affinity of the complex. Cell viability assay reveals that the toxicity of RATMP(C) in healthy HEK-293 cells could be reduced when it is loaded into liposomes. Both RATMP(C) and Lip-RATMP(C) do not show marked cytotoxic activity against A549 human lung adenocarcinoma and MCF-7 human breast carcinoma cells. But, Lip-RATMP(C) exhibits cytotoxic activity and apoptosis-inducing ability against HepG2 human liver carcinoma cells with a potency higher than that of the complex, illustrating the significance of formation of the liposome–Ru(arene) complex nanoaggregate. In contrast, RATMP(C) showed potent antibacterial activity against Pseudomonas aeruginosa, and Staphylococcus aureus, whereas Lip-RATMP(C) turned out to be inactive even in the higher concentration tested.