Comprehensive Computational Investigation of the Porphyrin-Based COF as a Nanocarrier for Delivering Anti-Cancer Drugs: A Combined MD Simulation and DFT Calculation

As nanomaterials have gained prominence in drug delivery technology, exploring their feasibility through computational methods is beneficial before practical tests. In this study, we aim to evaluate the capability of the porphyrin-based covalent organic framework COF-366 as a nanocarrier for two anticancer drugs, irinotecan (IRI) and doxorubicin (DOX). The optimal binding conformation of the drug molecules on the COF surface was predicted by using molecular docking. Subsequently, molecular dynamic simulation (MD) was performed to assess the adsorption mechanism of drug molecules on the COF in the aqueous environment. The free energy of adsorption for DOX and IRI was estimated to be −20.07 and −23.89 kcal/mol, respectively. The adsorption of both drugs on the COF surface is mainly influenced by the π–π interaction. Furthermore, density functional theory (DFT) calculation, natural bond orbital (NBO), and quantum theory of atoms in molecules (QTAIM) analyses were employed to investigate the structural stability of Drug@COF complexes and gain a detailed understanding of the interaction between them at the molecular level. Based on DFT results, it was found that in addition to π–π interaction, the bis-piperidine–phenylene interaction affects the adsorption of IRI on the COF surface. Moreover, the diffusion behavior of the drug molecule inside the COF pore was simulated using a ten-layer COF. Based on the mean square displacement analysis, the diffusion coefficients of DOX and IRI within the COF pore were calculated to be 108 and 97 um 2 /s, respectively. This computational study sheds light on how different types of interactions between the drug molecule and COF affect the adsorption and diffusion process. Our findings validated that the porphyrin-based COF-366 can serve as a nanobased platform for delivering DOX and IRI.