Determination of nanoparticle vehicle unpackaging by MR imaging of a T(2) magnetic relaxation switch.

Abstract

Non-invasive imaging of gene and drug delivery is an important tool in understanding the biodistribution and pharmacokinetics of vectors after in vivo administration. In this work, we demonstrate the utility of a multifunctional delivery vector comprised of polyethylenimine conjugated to ultrasmall, superparamagnetic iron oxide (USPIO). The conjugate (USPIO-PEI) is capable of complexing plasmid DNA into nanoparticles (SPIO-polyplex) with diameters approximately 100 nm and protecting the DNA from nuclease degradation. SPIO-polyplexes transfect cells with high efficiency and low toxicity. In addition, the T2 relaxation time of water enhanced by USPIO is shown to be a function of the packaging state of the vector. Thus, this material integrates capabilities of gene delivery with magnetic resonance (MR) contrast and also provides an MR-based read-out for vector unpackaging.