Microscopic machinery for ion-triggered drug release from gold nanoparticles-drug conjugates: Optical spectroscopy and molecular dynamics studies

Metal nanoparticle-drug binding, along with the controlled release of these drugs, plays a crucial role in the progress of personalized medicine. Understanding the intricate microscopic mechanisms that drive these processes holds the key to improving therapeutic results, especially since the efficiency of binding and unbinding can vary significantly depending on the specific drug payload and the perturbing agent used to trigger the release. We investigated the microscopic machinery that governs the controlled release of a specific cargo, vitamin B1 (VB1), conjugated with citrate-capped gold nanoparticles (cAuNPs), in response to externally added calcium ions (Ca^{2+}) in a sol of physiological pH. We employed optical spectroscopic techniques for our studies. Furthermore, to understand the drug-specific molecular interactions involved in the release of VB1 over hours/days, we designed a model based on classical molecular dynamics simulation. The results obtained from simulations and experiments reveal that the release of VB1 from the cAuNP-VB1 conjugate could be due to the stripping off and rearrangement of negatively charged citrate ions, which are a mediator of AuNP-VB1 binding, induced by Ca^{2+}. The investigation has been carried out on the benchtop and in silico for varying concentrations of Ca^{2+} ions. Essentially, this study offers a framework for understanding ion-induced drug release mechanisms, bridging experimental and theoretical approaches.