A Novel Nanoconjugate of Landomycin A with C₆₀ Fullerene for Cancer Targeted Therapy: In Vitro Studies

Landomycins are a subgroup of angucycline antibiotics that are produced by Streptomyces bacteria and possess strong antineoplastic potential. Literature data suggest that enhancement of the therapeutic activity of this drug may be achieved by means of creating specific drug delivery systems. Here we propose to adopt C₆₀ fullerene as flexible and stable nanocarrier for landomycin delivery into tumor cells.

The methods of molecular modelling, dynamic light scattering and Fourier transform infrared spectroscopy were used to study the assembly of C₆₀ fullerene and the anticancer drug Landomycin A (LA) in aqueous solution. Cytotoxic activity of this nanocomplex was studied in vitro towards two cancer cell lines in comparison to human mesenchymal stem cells (hMSCs) using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and a live/dead assay. The morphology of the cells incubated with fullerene-drug nanoparticles and their uptake into target cells were studied by scanning electron microscopy and fluorescence light microscopy.

The viability of primary cells (hMSCs, as a model for healthy cells) and cancer cell lines (human osteosarcoma cells, MG-63, and mouse mammary cells, 4T1, as models for cancer cells) was studied after incubation with water-soluble C₆₀ fullerenes, LA and the mixture C₆₀ + LA. The C₆₀ + LA nanocomplex in contrast to LA alone showed higher toxicity towards cancer cells and lower toxicity towards normal cells, whereas the water-soluble C₆₀ fullerenes at the same concentration were not toxic for the cells.

The obtained physico-chemical data indicate a complexation between the two compounds, leading to the formation of a C₆₀ + LA nanocomposite. It was concluded that immobilization of LA on C₆₀ fullerene enhances selectivity of action of this anticancer drug in vitro, indicating on possibility of further preclinical studies of novel C₆₀ + LA nanocomposites on animal tumor models.