Page - 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. Nadeau’s salary support was provided by the CanadaResearchChairs.DeveshBekah’sstipendwasprovidedby theNSERCCREATEMedicalPhysicsResearchTrainingNetwork (MPRTN). REFERENCES Alqathami,M.,Blencowe,A.,Yeo,U.,Franich,R.,Doran,S.,Qiao,G., et al. (eds.). (2013). Enhancement of radiation effects by bismuth oxide nanoparticles for kilovoltage x-ray beams: a dosimetric studyusing anovelmulti-compartment 3Dradiochromicdosimeter. J. Phys.Conf. Ser.444:012025. doi: 10.1088/1742- 6596/444/1/012025 Atkinson, R. L., Zhang, M., Diagaradjane, P., Peddibhotla, S., Contreras, A., Hilsenbeck, S.G., et al. (2010).Thermal enhancementwithoptically activated gold nanoshells sensitizes breast cancer stem cells to radiation therapy. Sci. Transl.Med.2:55ra79.doi:10.1126/scitranslmed.3001447 Babaei, M., and Ganjalikhani, M. (2014). The potential effectiveness of nanoparticles as radio sensitizers for radiotherapy. Bioimpacts 4, 15–20. doi: 10.5681/bi.2014.003 Brun, E., Sanche, L., and Sicard-Roselli, C. (2009). Parameters governing gold nanoparticle X-ray radiosensitization of DNA in solution. Colloids Surf B Biointerfaces72,128–134.doi:10.1016/j.colsurfb.2009.03.025 Bulin, A.-L., Truillet, C., Chouikrat, R., Lux, F., Frochot, C., Amans, D., et al. (2013). X-ray-induced singlet oxygen activation with nanoscintillator- coupled porphyrins. J. Phys. Chem. C 117, 21583–21589. doi: 10.1021/jp4 077189 Bünzli, J.-C. G., and Eliseeva, S. V. (2010). Basics of lanthanide photophysics. LanthanideLuminescence7,1–45.doi:10.1007/4243_2010_3 Butterworth, K. T., McMahon, S. J., Currell, F. J., and Prise, K. M. (2012). Physical basis and biologicalmechanisms of gold nanoparticle radiosensitiza- tion.Nanoscale4,4830–4838.doi:10.1039/c2nr31227a Cao, P., Tong, L., Hou, Y., Zhao, G., Guerin, G., Winnik, M. A., et al. (2012). Improving lanthanide nanocrystal colloidal stability in competitive aqueous buffer solutions using multivalent PEG-phosphonate ligands. Langmuir 28, 12861–12870.doi:10.1021/la302690h Chattopadhyay,N., Cai, Z. L., Kwon, Y. L., Lechtman, E., Pignol, J. P., andReilly, R.M. (2013).Molecularly targeted gold nanoparticles enhance the radiation response of breast cancer cells and tumor xenografts to X-radiation. Breast CancerRes.Treat.137,81–91.doi:10.1007/s10549-012-2338-4 Chen,W.,andZhang, J. (2006).Usingnanoparticles toenable simultaneousradia- tionandphotodynamictherapies forcancer treatment. J.Nanosci.Nanotechnol. 6,1159–1166.doi:10.1166/jnn.2006.327 Cheng, S. H., and Lo, L. W. (2011). Inorganic nanoparticles for enhanced photodynamic cancer therapy. Curr. Drug Discov. Technol. 8, 250–268. doi: 10.2174/157016311796798982 Cho, S. H., Jones, B. L., and Krishnan, S. (2009). The dosimetric feasibil- ity of gold nanoparticle-aided radiation therapy (GNRT) via brachytherapy using low-energy gamma-/x-ray sources.Phys.Med. Biol. 54, 4889–4905. doi: 10.1088/0031-9155/54/16/004 Di, W., Li, J., Shirahata, N., and Sakka, Y. (2010). An efficient and biocompatible fluorescence resonance energy transfer system based on lanthanide-dopednanoparticles.Nanotechnology21:455703.doi:10.1088/0957- 4484/21/45/455703 Diagaradjane, P., Shetty, A., Wang, J. C., Elliott, A. M., Schwartz, J., Shentu, S., et al. (2008). Modulation of in vivo tumor radiation response via gold nanoshell-mediated vascular-focused hyperthermia: characterizing an inte- grated antihypoxic and localized vascular disrupting targeting strategy.Nano Lett.8,1492–1500.doi:10.1021/nl080496z Dolmans,D.E., Fukumura,D., and Jain,R.K. (2003). Photodynamic therapy for cancer.Nat.Rev.Cancer3,380–387.doi:10.1038/nrc1071 Dorenbos, P. (2000). The 5d level positions of the trivalent lanthanides in inorganic compounds. J. Lumin. 91, 155–176. doi: 10.1016/S0022-2313(00) 00229-5 Dujardin, C., Amans, D., Belsky, A., Chaput, F., Ledoux, G., and Pillonnet, A. (2010).Luminescenceandscintillationpropertiesat thenanoscale. IEEETrans. Nucl. Sci.57,1348–1354.doi:10.1109/TNS.2009.2035697 Frontiers inChemistry | ChemicalEngineering October2014 |Volume2 |Article86 | 57