Therapeutic potential of CX (X = 48, 60, and 70) fullerenes as drug delivery carriers for ifosfamide anti-cancer drug

Abstract

Ifosfamide (ISF) has been known as an anticancer drug. It attacks fast growing cancer cells and unfortunately, it also attacks other quickly growing cells such as hair roots. Therefore, it is essential to find a method for delivering of this drug to the targeted tumor cells to reduce its side effects. To this aim, here, we applied a new kind of fullerenes to this purpose and introduce a new strategy based on the drug release in cancer cells. We studied the interaction of C48, C60, and C70 fullerenes with this drug using density functional theory calculations. Based on the results, the pure fullerenes are not suitable for the drug delivery of ISF because of a weak interaction. We found that Al doping into the C48, C60, and C70 leads to an increase in the ISF adhesion energy of from −4.3, −4.8, and − 5.3 kcal/mol to −28.2, −29.1, and − 30.7 kcal/mol, respectively. This shows that Al atom significantly increases the drug loading capacity and reactivity of fullerenes, making them more suitable for drug delivery. We introduced a drug release mechanism in cancerous tissues with a low pH. The strategy is based on the protonation of ISF, which separated it from the fullerene surface. The interaction mechanism of ISF with the fullerene changes from covalent to H-bonding in the acidic environment of cancerous cells. We also showed that the water solvent has a negligible effect on the adsorption process.