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

Mouli SK, Tyler P, McDevitt JL, Eifler AC, Guo Y, Nicolai J, Lewandowski RJ, Li W, Procissi D, Ryu RK, Wang YA, Salem R, Larson AC, Omary RA
ACS Nano. 2013 7 (9): 7724-33

PMID: 23952712 · PMCID: PMC4012535 · DOI:10.1021/nn4023119

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.

MeSH Terms (13)

Animals Antineoplastic Agents Cell Line, Tumor Doxorubicin Embolization, Therapeutic Magnetic Resonance Imaging, Interventional Magnetite Nanoparticles Male Neoplasms, Experimental Rabbits Rats Rats, Sprague-Dawley Treatment Outcome

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