Penetration of Antitumor Nucleotide–Actinomycin Nanocomplexes into Thymocytes

Abstract

Abstract—Spectrophotometry, spectrofluorimetry, IR spectroscopy, quasi-dark-field and fluorescence microscopy were used to investigate the conditions for penetration of the heterocyclic antitumor antibiotic actinomycin D (AMD) and its fluorescent derivative 7-amino-actinomycin D (7AAMD) into T cells (thymocytes) from the thymus of young rats. It has been shown that AMD and 7AAMD penetrate poorly into thymocytes. Therefore, when used as medicines, they do not suppress the cellular immunity necessary for cancer prevention. The penetration of AMD and 7AAMD into thymocytes increases with increasing concentration of the antibiotic and increasing duration of cell incubation at 37°C. Upon the addition of NAD (nicotinamide adenine dinucleotide), AMP (adenosine monophosphate), GMF (guanosine monophosphate) or caffeine (nucleotide analogues capable of forming nanocomplexes with an antibiotic), the occurrence of AMD and 7AAMD in thymocytes significantly increases. Therefore, cancer therapy with actinomycin antibiotics cannot be performed at high concentrations of these substances. On the other hand, the data on the increased occurrence of the antibiotic in the presence of nucleotide analogues suggest that the therapeutic concentration of the antibiotic can be reduced in their presence. These data can be used to treat lymphomas, leukemia, and other oncologic diseases. In this case, it will be useful to use NAD and other nucleotide analogues. The percentage of killed cells determined by trypan blue staining increases, especially when using NAD.