Evaluation of biocompatibility of magnetic silica nanoparticles and magnetic hyperthermia - induced drug release in a cell culture system

Mesoporous silica nanoparticles (MSN) have been extensively used in numerous effective therapeutic strategies as novel drug delivery systems. Their large loading capability, flexible surface modification and excellent... [ view full abstract ]

Mesoporous silica nanoparticles (MSN) have been extensively used in numerous effective therapeutic strategies as novel drug delivery systems. Their large loading capability, flexible surface modification and excellent biocompatibility are ideal properties for pharmaceutical drug carriers. However, there is an urgent need to improve MSN target specificity in vivo and to achieve subsequent controlled drug release at the target site. To address these questions we characterized a MSN-based drug delivery vehicle containing a Fe₃O₄ magnetic core. By subjecting these magnetic particles to an alternating magnetic field hyperthermia is produced. We proposed to combine magnetic core MSNs and thermo-sensitive linker surface modification to generate a novel drug delivery system. We have used different phagocytic cell lines and primary cells to investigate biocompatibility and efficient uptake. Upon subjecting cells loaded with magnetic core MSNs to an alternating magnetic field, magnetic hyperthermia is produced which induces cell death by an apoptotic pathway. We also show that the extent of cell death upon magnetic hyperthermia is cell line dependent with highest effect on primary cells. Next, an Ansamitocin derivative, as a model drug was linked to magnetic core MSNs via a thermo-sensitive linker. In vitro studies show that the drug can be cleaved from the particles upon exposure to magnetic field and drops the viability of exposed cells. Together our results indicate that controlled drug release from nanoparticles can be achieved upon exposure of cells to an alternating magnetic field.