Targeted delivery of amphotericin B to cells by using functionalized carbon nanotubes

Functionalized carbon nanotubes (f-CNTs) are attracting increasing attention as new vectors for the delivery of therapeutic molecules. In fact, carbon nanotubes (CNTs) have been shown to cross cell membranes easily and to deliver peptides, proteins, and nucleic acids into cells. These innovative carriers present a lower toxicity, a fact that boosts their potential for biomedical applications. The aim of the work here described was first to explore a new strategy for the double functionalization of CNTs, secondly, to assess the toxicity and uptake characteristics of CNTs functionalized with fluorescein and amphotericin B (AmB), an effective antifungal drug, which is however highly toxic to mammalian cells, and thirdly, to evaluate the antifungal activity of CNT–AmB conjugates. Conjugation of AmB to CNTs could have several advantages: i) increased solubility of the molecule with decreased aggregation phenomena that cause the high toxicity of the drug; ii) improved efficacy owing to the cell-penetrating capacity of the CNTs; and iii) modulation of the antifungal/toxic activity against different types of cells. The results obtained indicate that multiwalled carbon nanotubes functionalized with fluorescein isothiocyanate and amphotericin B (AmB), are rapidly internalized by mammalian cells without the toxic effects typically displayed upon treatment with unconjugated AmB. Furthermore, the modified drug exhibits a higher antifungal activity than native AmB.