Anti-Cancer Warfare: A New Hope. ReaxFF MDs Disclose the Stages of Biohybrid Nano Weapons Preparation, Structure, Dynamics, and Final Action.

Understanding the stability and functionality of nanocarriers in drug delivery systems is crucial to get effective therapeutic outcomes. In this work, we have conducted Reactive Molecular Dynamics simulations based on a tuned force field to investigate the assembly and behavior of a nanocarrier composed of a functionalized zinc oxide nanoparticle (ZnONP) loaded with an anti-cancer drug [1]. Our goal has been to gain new insights into the reactivity of the whole system and its ability to release the drug cargo in a physiological setting. The simulations revealed the intricate dynamics and interactions among the various components: for example, the functional chains (oleic acid) exhibited stable chemisorption on the ZnONP, forming monodentate or bidentate bonds with the metal oxide surface. These chains enhanced the stability and distribution of the lipid cover and acted as a reservoir for the drug molecules. The drug was entrapped within the lipid chains or adsorbed on the exposed surface regions, which could be detrimental to its release. Our findings demonstrated a gradual increase in the aggregate size due to the lipid cover's swelling in response to the aqueous medium. This evolution led to an unpacked structure with extended and separated lipid chains, providing potential pathways for a gradual drug release. This computational strategy successfully described and predicted the dynamics of the nanocarrier during various stages, in agreement with experimental results. It also showed how the possible reactions could be evaluated to predict the behavior of functionalized nano-vehicles in different environments, emphasizing the need to include reactivity for optimizing the nanocarrier design.