Seite - 57 - in Cancer Nanotheranostics - What Have We Learnd So Far?

Cooperet al. Nanoparticles for radiation therapy co-treatments. Gold nanoparticles are themost studied, though are not yet in the clinic for radiation therapy. Research efforts are underway to increase the efficiency of nanoparticle-based treatments, including physical and chemical optimization of nanoparticles, improved targeting such that total doses can be reduced, and combining ionizing radiation with other ther- apeutic modalities. Pre-sensitization of tumors with localized heating resulting from illumination of Au nanostructures with infrared light (photothermal therapy) has shown encouraging results. A number of less expensive alternatives to Au have been produced, but have not been subject to the same level of research activity. Oxides and selenides of Pt and Bi have been shown to provide radiation dose enhancement, while those of Gd andFe also enablemagnetism-based imaging, guidance and hyperthermia. Nanoscintillators consist of a broad class of nanostructures that emit light ranging from the ultraviolet to the infrared upon excitation by ionizing radiation, with spectra that depend primarily on composition. Energy transfer from excited state nanoscintillators to surface-attached photosensitizer molecules allows such a system to improve upon the issue of tissue trans- mittanceencounteredwith typicalPDT, combinedwith thedose enhancementprovidedby thedensenanoparticles. If theemitted light isofanappropriatewavelengthtobeabsorbedbyphotosen- sitizermolecules, nanoscintillator-photosensitizer bioconjugates have the potential to improve upon the issue of tissue transmit- tance with typical PDT. Such systems have only recently been reported, but represent anotherdistinct class for combined ther- apy that requires only ionizing radiation. As these systems have thus far only been studied in vitro, and cover many possible material compositions and drug varieties, it is difficult to reach definitive conclusions about their advantages and disadvantages compared toAu.While the rawmaterials are less expensive than Au in general, the particles tend to be less than half as dense as Au, and provide lower enhancement factors. While the sur- face chemistry of Au is well established and reliable, oxide and fluoride nanoscintillators have known colloidal stability issues. Certainly, if XRT and PDT effects are determined to be syn- ergistic, such systems may soon become a viable option for nanotherapeutics. Despite the substantial progress innanoparticle-assisted ther- apies in recent years, nanoscale radiosensitization effects have not yet been studied in great detail. Further understanding of the essential principles and interactions will help establish the legitimacy of new undertakings in the burgeoning field of nanomedicine, where clinical applications are just beginning to emerge. While a good deal of preclinical data on GNRT is avail- able, there are not yet clinical trials in the U.S. Two types of Au nanoparticles have been FDA approved for cancer tri- als: Au-tumor necrosis factor conjugates (clinicaltrials.gov, NCT00356980) and Au nanoshells for photothermal ther- apy (AuroLase, currently recruiting, NCT01679470 and NCT00848042 for lung cancer and head and neck cancer, respectively). Hafnium oxide particles are in clinical trials as radiation enhancers (NCT01433068, currently recruiting; drug nameNBTXR3). ACKNOWLEDGMENTS This work was funded by the CIHR Operating Grant MOP- 133500. Jay L. 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Sci.57,1348–1354.doi:10.1109/TNS.2009.2035697 Frontiers inChemistry | ChemicalEngineering October2014 |Volume2 |Article86 | 57