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Temperature-sensitive magnetic drug carriers for concurrent gemcitabine chemohyperthermia.

Kim DH, Guo Y, Zhang Z, Procissi D, Nicolai J, Omary RA, Larson AC
Adv Healthc Mater. 2014 3 (5): 714-24

PMID: 24574255 · PMCID: PMC4008717 · DOI:10.1002/adhm.201300209

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.

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MeSH Terms (15)

Animals Antimetabolites, Antineoplastic Cell Line, Tumor Cell Survival Cellulose Deoxycytidine Drug Carriers Hyperthermia, Induced Magnetite Nanoparticles Mice Mice, Inbred BALB C Mice, Nude Pancreatic Neoplasms Tissue Distribution Xenograft Model Antitumor Assays

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