In Vitro Setup for Determination of Nanoparticle-Mediated Magnetic Cell and Drug Accumulation in Tumor Spheroids under Flow Conditions

Superparamagnetic iron oxide nanoparticles (SPIONs) are used in nanomedicine as transporter systems for therapeutic cargos, or to magnetize cells to make them magnetically guidable. In cancer treatment, the site-directed delivery of chemotherapeutics or immune effector cells to the tumor can increase the therapeutic efficacy in the target region, and simultaneously reduce toxic side-effects in the rest of the body. To enable the transfer of new methods, such as the nanoparticle-mediated transport from bench to bedside, suitable experimental setups must be developed. In vivo, the SPIONs or SPION-loaded cells must be applied into the blood stream, to finally reach the tumor: consequently, targeting and treatment efficacy should be analyzed under conditions which are as close to in vivo as possible. Here, we established an in vitro method, including tumor spheroids placed in a chamber system under the influence of a magnetic field, and adapted to a peristaltic pump, to mimic the blood flow. This enabled us to analyze the magnetic capture and antitumor effects of magnetically targeted mitoxantrone and immune cells under dynamic conditions. We showed that the magnetic nanoparticle-mediated accumulation increased the anti-tumor effects, and reduced the unspecific distribution of both mitoxantrone and cells. Especially for nanomedical research, investigation of the site-specific targeting of particles, cells or drugs under circulation is important. We conclude that our in vitro setup improves the screening process of nanomedical candidates for cancer treatment.