Self-assembled xK1 rosette nanotube as a nanocarrier for chemotherapeutic drug molecules: a molecular dynamics study

Abstract

Chemotherapy is widely recognized as an effective treatment for various types of cancers, relying on chemotherapeutic drugs such as chlorambucil (CBL), camptothecin (CPT), doxorubicin (DOX), and flutamide (FLU) to inhibit cancer cell metastasis through their cytotoxic effects. However, these drugs also interact with noncancerous cells, causing significant side effects, including but not limited to nausea, vomiting, hair loss, peripheral neuropathy, lymphedema, and infertility. Developing nano-based drug vehicles is one approach to alleviate such adverse effects. This study introduces a three-ring-xK1-type rosette nanotube (RNT) as a potential nano-based drug-delivery vehicle for these chemotherapeutic agents. Molecular dynamics (MD) simulations aided by the molecular mechanics/three dimensional reference interaction site model (MM/3DRISM) analysis were employed to evaluate the potential of xK1 as a drug carrier. Results revealed that xK1 exhibited structural stability and strong binding affinity with the selected drugs under physiological conditions, with binding energies ranging from −4.66 to −26.10 kcal mol⁻¹. The drugs favorably bind at either end of xK1 due to the prominent aromatic rings facilitating π–π stacking interactions. Furthermore, MD simulations of the release mechanism revealed structural disassembly, validating the responsiveness of the systems under acidic conditions. The findings here offer insights into the viability of xK1 for targeted drug delivery, which warrants further experimental studies.