Molecular dynamics insight of interaction between the functionalized-carbon nanotube and cancerous cell membrane in doxorubicin delivery

Background and objective: Doxorubicin (DOX) is a known anticancer drug which is widely used in cancer therapy. Carbon nanotubes (CNTs) are among the most promising platforms for smart drug delivery appli-cations. However, due to the toxicity and their low sulubility their application is limited and their func-tionalization with wide range of biomolecules are suggested. Therefore, the functionalized carbon nan-otubes (f-CNT) with carboxyl (CNT-COO) and folic acid (CNT-COO-FA) were investigated as drug-carrier.Methods: Molecular dynamics (MD) simulation along with the Density Functional Theory (DFT) methods are being used to study the drug loading process on functionalized carbon nanotubes.Results: The results indicate that doxorubicin molecules interact more with CNT-COO-FA than CNT-COO. The embedded dipalmitoylphosphatidylcholine (DPPC) lipid bilayer with a folate receptor was considered a cancerous cell's representative model. Then the drug release from the f-CNTs near the lipid bilayer was simulated. The results showed that CNT-COO-FA with a pH and ligand-sensitive mechanism strongly inter-acts with cancerous cells, which led to higher drug release, in agreement with the experimental results. The conformational changes of the lipid bilayer and folate receptor during drug release were evaluated. The analysis showed that drug release from CNT-COO-FA has significantly changed lipid bilayer and re-ceptor conformations. The obtained results were interpreted and justified by considering the molecular mechanisms which control the drug delivery in the studied systems.Conclusions: Based on the obtained results, CNT-COO-FA has a better performance during the drug release compared to CNT-COO in delivering doxorubicin. Both pH and ligand sensitive mechanisms are found to be responsible for higher drug delivery efficiency of CNT-COO-FA. In contrast, CNT-COO can only enhance drug delivery efficiently with a pH-sensitive mechanism.(c) 2022 Elsevier B.V. All rights reserved.