Image-guided local delivery strategies enhance therapeutic nanoparticle uptake in solid tumors

SK Mouli, P Tyler, JL McDevitt, AC Eifler, Y Guo… - ACS …, 2013 - ACS Publications
SK Mouli, P Tyler, JL McDevitt, AC Eifler, Y Guo, J Nicolai, RJ Lewandowski, W Li, D Procissi
ACS nano, 2013ACS Publications
Nanoparticles (NP) have emerged as a novel class of therapeutic agents that overcome
many of the limitations of current cancer chemotherapeutics. However, a major challenge to
many current NP platforms is unfavorable biodistribution, and limited tumor uptake, upon
systemic delivery. Delivery, therefore, remains a critical barrier to widespread clinical
adoption of NP therapeutics. To overcome these limitations, we have adapted the
techniques of image-guided local drug delivery to develop nanoablation and …
Nanoparticles (NP) have emerged as a novel class of therapeutic agents that overcome many of the limitations of current cancer chemotherapeutics. However, a major challenge to many current NP platforms is unfavorable biodistribution, and limited tumor uptake, upon systemic delivery. Delivery, therefore, remains a critical barrier to widespread clinical adoption of NP therapeutics. To overcome these limitations, we have adapted the techniques of image-guided local drug delivery to develop nanoablation and nanoembolization. Nanoablation is a tumor ablative strategy that employs image-guided placement of electrodes into tumor tissue to electroporate tumor cells, resulting in a rapid influx of NPs that is not dependent on cellular uptake machinery or stage of the cell cycle. Nanoembolization involves the image-guided delivery of NPs and embolic agents directly into the blood supply of tumors. We describe the design and testing of our innovative local delivery strategies using doxorubicin-functionalized superparamagnetic iron oxide nanoparticles (DOX-SPIOs) in cell culture, and the N1S1 hepatoma and VX2 tumor models, imaged by high resolution 7T MRI. We demonstrate that local delivery techniques result in significantly increased intratumoral DOX-SPIO uptake, with limited off-target delivery in tumor-bearing animal models. The techniques described are versatile enough to be extended to any NP platform, targeting any solid organ malignancy that can be accessed via imaging guidance.
ACS Publications
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