Formulation and In Vitro Characterization of Composite Biodegradable Magnetic Nanoparticles for Magnetically Guided Cell Delivery

Abstract

Cells modified with magnetically responsive nanoparticles (MNP) can provide the basis for novel targeted therapeutic strategies. However, improvements are required in the MNP design and cell treatment protocols to provide adequate magnetic properties in balance with acceptable cell viability and function. This study focused on select variables controlling the uptake and cell compatibility of biodegradable polymer-based MNP in cultured endothelial cells. Fluorescent-labeled MNP were formed using magnetite and polylactide as structural components. Their magnetically driven sedimentation and uptake were studied fluorimetrically relative to cell viability in comparison to non-magnetic control conditions. The utility of surface-activated MNP forming affinity complexes with replication-deficient adenovirus (Ad) for transduction achieved concomitantly with magnetic cell loading was examined using the green fluorescent protein reporter. A high-gradient magnetic field was essential for sedimentation and cell binding of albumin-stabilized MNP, the latter being rate-limiting in the MNP loading process. Cell loading up to 160 pg iron oxide per cell was achievable with cell viability >90%. Magnetically driven uptake of MNP-Ad complexes can provide high levels of transgene expression potentially useful for a combined cell/gene therapy. Magnetically responsive endothelial cells for targeted delivery applications can be obtained rapidly and efficiently using composite biodegradable MNP.