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Our study demonstrated the potential to optimize superparamagnetic iron oxide content for future studies intending to quantify intrahepatic yttrium 90 microsphere delivery in clinical settings.

To improve the efficacy of gemcitabine (GEM) for the treatment of advanced pancreatic cancer via local hyperthermia potentiated via a multi‐functional nanoplatform permitting both in vivo heating and drug delivery is the goal of this study. Here, a chemohyperthermia approach to synergistically achieve high intra‐tumoral drug concentrations, while permitting concurrent hyperthermia for more effective tumor cell kill and growth inhibition, is proposed. Drug delivery and hyperthermia are achieved using a hydroxypropyl cellulose (HPC)‐grafted porous magnetic drug carrier that is MRI visible to permit in vivo visualization of the biodistribution. These synthesized magnetic drug carriers produce strong T2‐weighted image contrast and permit efficient heating using low‐magnetic‐field intensities. The thermomechanical response of HPC permits triggered GEM release confirmed during in vitro drug release studies. During in vitro studies, pancreatic cancer cell growth is significantly inhibited (≈82% reduction) with chemohyperthermia compared to chemotherapy or hyperthermia alone. Using PANC‐1 xenografts in nude mice, the delivery of injected GEM‐loaded magnetic carriers (GEM‐magnetic carriers) is visualized with both MRI and fluorescent imaging techniques. Chemohyperthermia with intra‐tumoral injections of GEM‐magnetic carriers (followed by heating) results in significant increases in apoptotic cell death compared to tumors treated with GEM‐magnetic carriers injections alone. Chemohyperthermia with GEM‐magnetic carriers offers the potential to significantly improve the therapeutic efficacy of GEM for the treatment of pancreatic cancer. In vivo delivery confirmation with non‐invasive imaging techniques could permit patient‐specific adjustments therapeutic regimens for improve longitudinal outcomes. An effective chemohyperthermia approachto synergistically achieve high intra‐tumoral drug concentrationswhile permitting concurrent hyperthermia is enabled by a hydroxypropyl cellulose grafted porous magnetic drug carrier. These initial encouraging results suggest that chemohyperthermia with gemcitabine‐loaded temperature‐sensitive magnetic carriers may offer an innovative new approach for more effective treatment of pancreatic cancer.

After inducing McA tumors in Sprague-Dawley rats (McA-SD), the following hypotheses were tested: first, that hypervascular McA tumors grown in Sprague-Dawley rats provide a suitable platform to investigate drug delivery; and second, that high-field MRI can be used to measure intratumoral uptake of DOX-SPIOs.

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 viaimaging guidance.

Electropermeabilization involves the application of electrical pulses to increase cell membrane permeability. The purpose of our study was to demonstrate the potential to use electroporation-mediated transcatheter arterial chemoembolization (E-TACE) approaches to increase liver tumor drug uptake while using magnetic resonance imaging (MRI) for intraprocedural optimization of these procedures.