Understanding the Effect of Functionalization on Loading Capacity and Release of Drug from Mesoporous Silica Nanoparticles: A Computationally Driven Study

[Image: see text] MCM-41, a type of mesoporous silica nanoparticle, has garnered widespread interests as a useful carrier for drug delivery wherein the drug gets adsorbed into the pores of the carrier. To understand the adsorption mechanism and release of the drug at the molecular level, in the current study, it was attempted to generate a computational model for the loading of 5-fluorouracil (5-FU), a chemotherapeutic agent into surface-modified MCM-41. The molecular surface models of the mesoporous silica (MCM-41) nanoparticle with different surface substitutions were created. In the first stage, molecular mechanics (MM) simulations were carried out to obtain the optimized surface structures. Subsequently, a 5-FU drug molecule in its different forms was docked on top of different MCM-41 surfaces to understand the adsorption orientation and energetics. To further validate the results, more accurate quantum mechanical (QM) calculations were also carried out, and the energetics between the QM and MM calculations are found to be similar. All the substitutions (−NH(2), −CN, −COOH) except the methyl substitution exhibited favorable interactions compared to the unsubstituted MCM-41 surface which was in accordance with the experimental observations. The release rate of 5-FU from MCM-41 and aminopropyl-substituted MCM-41 (MCM-NH(2)) was studied using molecular dynamics simulations which revealed that the release rate of 5-FU from the MCM-NH(2) surface was slower compared to that of plain MCM-41. The detailed surface characteristics and the adsorption energies from the molecular simulations correlating the loading capacity and release are reported in here.