Targeted Nanoparticles And Imaging Of Cancer

Hofmann and collaborators have evaluated the ability of super paramagnetic iron oxide nanoparticles (SPION) to interact with human melanoma cells in such a way that these particles could be selectively targeted to tumor cells ands then imaged using MRI.74 They varied the coating placed on these particles and found that when comparing particles coated with poly(vinyl alcohol) (PVA), a vinyl alcohol/vinyl amine copolymer (amine-SPION), PVA with randomly distributed carboxylic groups or PVA with randomly distributed thiol groups, human cells in culture would interact strongly only with the amine-SPION particles. Furthermore, these particles showed the lowest cytotoxicity.

This human study involved intravenous administration of Combidex (Advanced Magnetics, Inc., ferumoxtran-10, a molecular imaging agent of iron oxide nanoparticles and a dense packing of dextran derivatives) to 18 men ages 21-46 with diagnosed testicular cancer.75 The Combidex was imaged using MRI. From this study, it seems evident that those lymph nodes with a higher signal were classified as being malignant. However, based on the information from Advanced Magnetics, these particles should accumulate selectively in noncancerous lymph node tissue. The particles are still experimental and rightly so.

Although treatment of cancer with targeted nanoparticles is an important goal, more accurate imaging of cancer is needed to allow for the optimal treatment for each patient. Towards that end, a considerable amount of research is underway with various imaging techniques to establish more accurate determination of the presence and extent of cancer growth and metastases. Because magnetic resonance imaging (MRI) is a widely used imaging technique, much work is currently being done to develop targeted imaging agents for MRI. Some of these involve paramagnetic and superparamagnetic iron oxides due to their ability to affect water relaxation times Tj and T2. Gasco and collaborators have prepared solid lipid nanoparticles containing Endorem, superparamagnetic iron oxide nanopar-ticles (Guebert and Advanced Magnetics), using either a multiple emulsion technique or an oil in water emulsion technique.76 Although the loading rates achieved were less than 1 wt% iron, it was possible to detect and image in vivo in rats. Incorporation of the Endorem in the SLN allowed passage across the blood brain barrier, passage which was not possible with Endorem alone.

Often development of nanoparticle systems is a two-pronged approach involving both drug and imaging agent. If a targeting system is successful, one should be able to enhance the imaging of a cancer and then kill it with the same system. One such study involved the preparation of glycol-chitosan nanoaggregates to which either fluorescein isothiocyanate (FITC) or doxorubicin (Dox) was conjugated.12 Based on a single tail-vein injection of FITC-conjugates, levels remained high for eight days and gradually increased in the tumors of rats with II45 mesothelioma cells, in the kidney, and to a lesser extent in the spleen. Meanwhile, levels decreased in other organs. The liver showed some accumulation at day 3 but was significantly lower at day 8 relative to days 1 and 3. The performance of these systems, as evidenced by a decrease in tumor volume, was excellent with a consistent decrease in tumor volume after day 13 when a tail-vein injection of Dox-nanoaggregates is given at days 13 and 19.

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