Fullerene as a doxorubicin nanotransporter for targeted breast cancer therapy: Capillary electrophoresis analysis

Abstract

The clinical use of doxorubicin (DOX) is limited by dose-related cardiomyopathy, which becomes more prevalent with increasing cumulative doses of the drug. Complexes of fullerene with DOX were designed and studied using biophysical methods. The ability of DOX to release from fullerene at different pHs was analyzed. It has been shown that the size of the fullerene-DOX complexes was ∼280 nm. The zeta potential for fullerene was -30 mV, for DOX -8 mV, and for fullerene-DOX conjugates -24 mV. Drug release was studied by CE with LIF detection. When fullerene-DOX conjugates were separated in a pH 7.5 buffer, 43% of all DOX signals were derived from free DOX, with the signal increasing as pH decreased. At pH 5.25, all DOX had been released and 100% of the signal was derived from free DOX. The release of DOX from complexes with fullerene at lower pH can be used in targeted antineoplastic therapy, resulting in lower toxicity for less acidic non-target tissue.

Metallothionein and Superoxide Dismutase—Antioxidative Protein Status in Fullerene-Doxorubicin Delivery to MCF-7 Human Breast Cancer Cells

“…Fullerenes (C 60 ), due to their special physico-chemical properties, make great candidates for drug transporters [ 22 ]. The difference in their size measured by scanning electron microscopy and by dynamic light scattering was discussed in our previous work and obtained data are in agreement with other reports, in which the fullerene size is between 150−490 nm [ 11 ]. The structure of C 60 enabling the adoption of up to six electrons indicates the possible antioxidant effect of this form of carbon [ 23 ].…”

“…Complexes of fullerene (C 60 ) with DOX were prepared according to previous protocol [ 11 ]. Briefly, C 60 (12.5 or 25 mg) in 4 mL of HNO 3 :H 2 SO 4 (1:3) mixture was dispersed and heated for 7 h at 70 °C.…”

“…The morphology of complexes was assessed using scanning electron microscopy as stated before [ 11 ]. Experiments were conducted by depositing 10 μL of aqueous solutions of the fullerene and C 60 –DOX complexes on a freshly cleaved mica grid and allowing them to dry for 60 min in air.…”

“…This property is attributed to the small size of these carbon molecules, thanks to which they may use the so-called enhanced permeability and retention effect (EPR), which means that they penetrate easily through the less-tight blood vessels nourishing the cancer [ 10 ]. The use of a nanotransporter makes it possible to regulate the release of the coupled drug, breaking the drug-transporter binding at a suitable pH, e.g., a cancer cell that is characteristic of the environment [ 11 ]. These actions ensure a selective accumulation of the drug in the tumor and significantly reduce the amount necessary to obtain a therapeutic effect.…”

Cytotoxicity of doxorubicin conjugated with C60 fullerene. Structural and in vitro studies

“…Both van der Waals (vdW) complexes between the delivered drugs and a fullerene as well as fullerene-drug covalent conjugates were considered for this purpose. For instance, fullerene-DOX complexes, in which the release of DOX was pH-dependent, were prepared and characterized with capillary electrophoresis [16]. Similarly, a complex of fullerene-based carrier with cisplatin (well-known anticancer agents) was tested against lung cancer [17].…”