X-ray sensitive high-Z metal nanocrystals for cancer imaging and therapy

Polgár, C.; Ott, O. J.; Hildebrandt, G.; Kauer-Dorner, D.; Knauerhase, H.; Major, T.; Lyczek, J.; Guinot, J. L.; Dunst, J.; Miguelez, C. G. et al. Late side-effects and cosmetic results of accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2017, 18, 259–268.

Barton, M. B.; Jacob, S.; Shafiq, J.; Wong, K.; Thompson, S. R.; Hanna, T. P.; Delaney, G. P. Estimating the demand for radiotherapy from the evidence: A review of changes from 2003 to 2012. Radiother. Oncol. 2014, 112, 140–144.

Baumann, M.; Krause, M.; Overgaard, J.; Debus, J.; Bentzen, S. M.; Daartz, J.; Richter, C.; Zips, D.; Bortfeld, T. Radiation oncology in the era of precision medicine. Nat. Rev. Cancer 2016, 16, 234–249.

Benderitter, M.; Caviggioli, F.; Chapel, A.; Coppes, R. P.; Guha, C.; Klinger, M.; Malard, O.; Stewart, F.; Tamarat, R.; Van Luijk, P. et al. Stem cell therapies for the treatment of radiation-induced normal tissue side effects. Antioxid. Redox Signal. 2014, 21, 338–355.

Brown, J. M.; Wilson, W. R. Exploiting tumour hypoxia in cancer treatment. Nat. Rev. Cancer 2004, 4, 437–447.

Liu, J. N.; Bu, W. B.; Shi, J. L. Chemical design and synthesis of functionalized probes for imaging and treating tumor hypoxia. Chem. Rev. 2017, 117, 6160–6224.

Song, G. S.; Cheng, L.; Chao, Y.; Yang, K.; Liu, Z. Emerging nanotechnology and advanced materials for cancer radiation therapy. Adv. Mater. 2017, 29, 1700996.

Gaikwad, H. K.; Tsvirkun, D.; Ben-Nun, Y.; Merquiol, E.; Popovtzer, R.; Blum, G. Molecular imaging of cancer using X-ray computed tomography with protease targeted iodinated activity-based probes. Nano Lett. 2018, 18, 1582–1591.

Tsvirkun, D.; Ben-Nun, Y.; Merquiol, E.; Zlotver, I.; Meir, K.; Weiss-Sadan, T.; Matok, I.; Popovtzer, R.; Blum, G. CT imaging of enzymatic activity in cancer using covalent probes reveal a size-dependent pattern. J. Am. Chem. Soc. 2018, 140, 12010–12020.

Shen, S. D.; Chao, Y.; Dong, Z. L.; Wang, G. L.; Yi, X.; Song, G. S.; Yang, K.; Liu, Z.; Cheng, L. Bottom-up preparation of uniform ultrathin rhenium disulfide nanosheets for image-guided photothermal radiotherapy. Adv. Funct. Mater. 2017, 27, 1700250.

Ding, H.; Yong, K. T.; Roy, I.; Pudavar, H. E.; Law, W. C.; Bergey, E. J.; Prasad, P. N. Gold nanorods coated with multilayer polyelectrolyte as contrast agents for multimodal imaging. J. Phys. Chem. C 2007, 111, 12552–12557.

Hu, X. G.; Gao, X. H. Multilayer coating of goldnanorods for combined stability and biocompatibility. Phys. Chem. Chem. Phys. 2011, 13, 10028–10035.

Liu, W. J.; Zhu, Z. N.; Deng, K.; Li, Z. T.; Zhou, Y. L.; Qu, H. B.; Gao, Y.; Che, S. A.; Tang, Z. Y. Gold nanorod@chiral mesoporous silica core–shell nanoparticles with unique optical properties. J. Am. Chem. Soc. 2013, 135, 9659–9664.

Conde, J.; Doria, G.; Baptista, P. Noble metal nanoparticles applications in cancer. J. Drug. Deliv. 2012, 2012, 751075.

Cao-Milán, R.; Liz-Marzán, L. M. Gold nanoparticle conjugates: Recent advances toward clinical applications. Expert Opin. Drug Deliv. 2014, 11, 741–752.

Kyriakou, Y.; Riedel, T.; Kalender, W. A. Combining deterministic and monte carlo calculations for fast estimation of scatter intensities in CT. Phys. Med. Biol. 2006, 51, 4567.

Lusic, H.; Grinstaff, M. W. X-ray computed tomography contrast agents. Chem. Rev. 2013, 113, 1641–1666.

Kinsella, J. M.; Jimenez, R. E.; Karmali, P. P.; Rush, A. M.; Kotamraju, V. R.; Gianneschi, N. C.; Ruoslahti, E.; Stupack, D.; Sailor, M. J. X-ray computed tomography imaging of breast cancer by using targeted peptide-labeled bismuth sulfide nanoparticles. Angew. Chem. , Int. Ed. 2011, 50, 12308–12311.

Matsudaira, H.; Ueno, A. M.; Furuno, I. Iodine contrast medium sensitizes cultured mammalian cells to X rays but not to γ rays. Radiat. Res. 1980, 84, 144–148.

Iwamoto, K. S.; Cochran, S. T.; Winter, J.; Holburt, E.; Higashida, R. T.; Norman, A. Radiation dose enhancement therapy with iodine in rabbit VX-2 brain tumors. Radiother. Oncol. 1987, 8, 161–170.

Brun, E.; Sicard-Roselli, C. Actual questions raised by nanoparticle radiosensitization. Radiat. Phys. Chem. 2016, 128, 134–142.

Butterworth, K. T.; McMahon, S. J.; Currell, F. J.; Prise, K. M. Physical basis and biological mechanisms of gold nanoparticle radiosensitization. Nanoscale 2012, 4, 4830–4838.

Cormode, D. P.; Naha, P. C.; Fayad, Z. A. Nanoparticle contrast agents for computed tomography: A focus on micelles. Contrast Media Mol. Imaging 2014, 9, 37–52.

Jakhmola, A.; Anton, N.; Vandamme, T. F. Inorganic nanoparticles based contrast agents for x-ray computed tomography. Adv. Healthc. Mater. 2012, 1, 413–431.

Herold, D. M.; Das, I. J.; Stobbe, C. C.; Iyer, R. V.; Chapman, J. D. Gold microspheres: A selective technique for producing biologically effective dose enhancement. Int. J. Radiat. Biol. 2000, 76, 1357– 1364.

Idé, J. M.; Lancelot, E.; Pines, E.; Corot, C. Prophylaxis of iodinated contrast media-induced nephropathy: A pharmacological point of view. Invest. Radiol. 2004, 39, 155–170.

Hainfeld, J. F.; Slatkin, D. N.; Smilowitz, H. M. The use of gold nanoparticles to enhance radiotherapy in mice. Phys. Med. Biol. 2004, 49, N309–N315.

Joh, D. Y.; Sun, L.; Stangl, M.; Al Zaki, A.; Murty, S.; Santoiemma, P. P.; Davis, J. J.; Baumann, B. C.; Alonso-Basanta, M.; Bhang, D. et al. Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization. PLoS One 2013, 8, e62425.

Tao, Y.; Li, M. Q.; Liu, X. Y.; Leong, K. W.; Gautier, J.; Zha, S. Dual-color plasmonic nanosensor for radiation dosimetry. ACS Appl. Mater. Interfaces 2020, 12, 22499–22506.

Ma, N. N.; Wu, F. G.; Zhang, X. D.; Jiang, Y. W.; Jia, H. R.; Wang, H. Y.; Li, Y. H.; Liu, P. D.; Gu, N.; Chen, Z. Shape-dependent radiosensitization effect of gold nanostructures in cancer radiotherapy: Comparison of gold nanoparticles, nanospikes, and nanorods. ACS Appl. Mater. Interfaces 2017, 9, 13037–13048.

Bhattarai, S. R.; Derry, P. J.; Aziz, K.; Singh, P. K.; Khoo, A. M.; Chadha, A. S.; Liopo, A.; Zubarev, E. R.; Krishnan, S. Gold nanotriangles: Scale up and X-ray radiosensitization effects in mice. Nanoscale 2017, 9, 5085–5093.

Zhang, A. W.; Guo, W. H.; Qi, Y. F.; Wang, J. Z.; Ma, X. X.; Yu, D. X. Synergistic effects of gold nanocages in hyperthermia and radiotherapy treatment. Nanoscale Res. Lett. 2016, 11, 279.

Pei, L. H.; Mori, K.; Adachi, M. Direct chemical synthesis of gold nanowires with 2-D network structure and relationship between the presence of gold ions and shape stability of gold nanowires. Chem. Lett. 2004, 33, 324–325.

Pei, L. H.; Mori, K.; Adachi, M. Formation process of two-dimensional networked gold nanowires by citrate reduction of AuCl₄^– and the shape stabilization. Langmuir 2004, 20, 7837–7843.

Chithrani, B. D.; Chan, W. C. W. Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Lett. 2007, 7, 1542–1550.

Zou, R. X.; Guo, X.; Yang, J.; Li, D. D.; Peng, F.; Zhang, L.; Wang, H. J.; Yu, H. Selective etching of gold nanorods by ferric chloride at room temperature. Crystengcomm 2009, 11, 2797–2803.

Zhu, D. M.; Lyu, M.; Huang, Q. Q.; Suo, M.; Liu, Y.; Jiang, W.; Duo, Y. H.; Fan, K. L. Stellate plasmonic exosomes for penetrative targeting tumor NIR-Ⅱ thermo-radiotherapy. ACS Appl. Mater. Interfaces 2020, 12, 36928–36937.

Baffou, G.; Quidant, R.; Girard, C. Heat generation in plasmonic nanostructures: Influence of morphology. Appl. Phys. Lett. 2009, 94, 153109.

Hao, F.; Nehl, C. L.; Hafner, J. H.; Nordlander, P. Plasmon resonances of a gold nanostar. Nano Lett. 2007, 7, 729–732.

Lee, J.; Chatterjee, D. K.; Lee, M. H.; Krishnan, S. Gold nanoparticles in breast cancer treatment: Promise and potential pitfalls. Cancer Lett. 2014, 347, 46–53.

Wang, S. M.; Dai, Z. F.; Ke, H. T.; Qu, E. Z.; Qi, X. X.; Zhang, K.; Wang, J. R. Contrast ultrasound-guided photothermal therapy using gold nanoshelled microcapsules in breast cancer. Eur. J. Radiol. 2014, 83, 117–122.

Yavuz, M. S.; Cheng, Y. Y.; Chen, J. Y.; Cobley, C. M.; Zhang, Q.; Rycenga, M.; Xie, J. W.; Kim, C.; Song, K. H.; Schwartz, A. G. et al. Gold nanocages covered by smart polymers for controlled release with near-infrared light. Nat. Mater. 2009, 8, 935–939.

Rodríguez-Fernández, J.; Pérez-Juste, J.; de Abajo, F. J. G.; Liz-Marzán, L. M. Seeded growth of submicron au colloids with quadrupole plasmon resonance modes. Langmuir 2006, 22, 7007–7010.

Kumar, R.; Korideck, H.; Ngwa, W.; Berbeco, R. I.; Makrigiorgos, G. M.; Sridhar, S. Third generation gold nanoplatform optimized for radiation therapy. Transl. Cancer Res. 2013, 2, 228–239.

Perrault, S. D.; Walkey, C.; Jennings, T.; Fischer, H. C.; Chan, W. C. W. Mediating tumor targeting efficiency of nanoparticles through design. Nano Lett. 2009, 9, 1909–1915.

Wong, C.; Stylianopoulos, T.; Cui, J.; Martin, J.; Chauhan, V. P.; Jiang, W.; Popović, Z.; Jain, R. K.; Bawendi, M. G.; Fukumura, D. Multistage nanoparticle delivery system for deep penetration into tumor tissue. Proc. Natl. Acad. Sci. USA 2011, 108, 2426–2431.

Chithrani, D. B.; Jelveh, S.; Jalali, F.; van Prooijen, M.; Allen, C.; Bristow, R. G.; Hill, R. P.; Jaffray, D. A. Gold nanoparticles as radiation sensitizers in cancer therapy. Radiat. Res. 2010, 173, 719–728.

Chithrani, B. D.; Ghazani, A. A.; Chan, W. C. W. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 2006, 6, 662–668.

Khademi, S.; Sarkar, S.; Kharrazi, S.; Amini, S. M.; Shakeri-Zadeh, A.; Ay, M. R.; Ghadiri, H. Evaluation of size, morphology, concentration, and surface effect of gold nanoparticles on X-ray attenuation in computed tomography. Phys. Med. 2018, 45, 127–133.

Dou, Y.; Guo, Y. Y.; Li, X. D.; Li, X.; Wang, S.; Wang, L.; Lv, G. X.; Zhang, X. N.; Wang, H. J.; Gong, X. Q. et al. Size-tuning ionization to optimize gold nanoparticles for simultaneous enhanced CT imaging and radiotherapy. ACS Nano 2016, 10, 2536–2548.

Zhang, X. D.; Chen, J.; Luo, Z. T.; Wu, D.; Shen, X.; Song, S. S.; Sun, Y. M.; Liu, P. X.; Zhao, J.; Huo, S. D. et al. Enhanced tumor accumulation of sub-2 nm gold nanoclusters for cancer radiation therapy. Adv. Healthc. Mater. 2014, 3, 133–141.

Luo, D.; Wang, X. N.; Zeng, S.; Ramamurthy, G.; Burda, C.; Basilion, J. P. Targeted gold nanocluster-enhanced radiotherapy of prostate cancer. Small 2019, 15, 1900968.

Alqathami, M.; Blencowe, A.; Yeo, U. J.; Franich, R.; Doran, S.; Qiao, G.; Geso, M. Enhancement of radiation effects by bismuth oxide nanoparticles for kilovoltage X-ray beams: A dosimetric study using a novel multi-compartment 3D radiochromic dosimeter. J. Phys. : Conf. Ser. 2013, 444, 012025.

Hossain, M.; Su, M. Nanoparticle location and material-dependent dose enhancement in X-ray radiation therapy. J. Phys. Chem. C 2012, 116, 23047–23052.

Ma, G. C.; Liu, X. J.; Deng, G. Y.; Yuan, H. K.; Wang, Q. G.; Lu, J. A novel theranostic agent based on porous bismuth nanosphere for CT imaging-guided combined chemo-photothermal therapy and radiotherapy. J. Mater. Chem. B 2018, 6, 6788–6795.

Bulmahn, J. C.; Tikhonowski, G.; Popov, A. A.; Kuzmin, A.; Klimentov, S. M.; Kabashin, A. V.; Prasad, P. N. Laser-ablative synthesis of stable aqueous solutions of elemental bismuth nanoparticles for multimodal theranostic applications. Nanomaterials 2020, 10, 1463.

Rabin, O.; Manuel Perez, J.; Grimm, J.; Wojtkiewicz, G.; Weissleder, R. An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat. Mater. 2006, 5, 118–122.

Ai, K. L.; Liu, Y. L.; Liu, J. H.; Yuan, Q. H.; He, Y. Y.; Lu, L. H. Large-scale synthesis of Bi₂S₃ nanodots as a contrast agent for in vivo X-ray computed tomography imaging. Adv. Mater. 2011, 23, 4886– 4891.

Zhu, H. L.; Cheng, Q. Y.; Liao, M. Y.; Zhang, Z. L.; Cai, W. G.; Ma, J. J.; Sun, M. Y.; Yu, M. X.; Tian, Z. Q.; Pang, D. W. Economical synthesis of ultra-small Bi₂S₃ nanoparticles for high-sensitive CT imaging. Mater. Res. Express 2019, 6, 095005.

Du, F. Y.; Lou, J. M.; Jiang, R.; Fang, Z. Z.; Zhao, X. F.; Niu, Y. Y.; Zou, S. Q.; Zhang, M. M.; Gong, A. H.; Wu, C. Y. Hyaluronic acid-functionalized bismuth oxide nanoparticles for computed tomography imaging-guided radiotherapy of tumor. Int. J. Nanomedicine 2017, 12, 5973–5992.

Zhang, C. Y.; Yan, L.; Gu, Z. J.; Zhao, Y. L. Strategies based on metal-based nanoparticles for hypoxic-tumor radiotherapy. Chem. Sci. 2019, 10, 6932–6943.

Zhou, R. Y.; Wang, H. M.; Yang, Y. F.; Zhang, C. Y.; Dong, X. H.; Du, J. F.; Yan, L.; Zhang, G. J.; Gu, Z. J.; Zhao, Y. L. Tumor microenvironment-manipulated radiocatalytic sensitizer based on bismuth heteropolytungstate for radiotherapy enhancement. Biomaterials 2019, 189, 11–22.

Maggiorella, L.; Barouch, G.; Devaux, C.; Pottier, A.; Deutsch, E.; Bourhis, J.; Borghi, E.; Levy, L. 2001 ORAL nanoscale radiotherapy-NBTXR3 hafnium oxide nanoparticles as promising cancer therapy. Eur. J. Cancer 2011, 47, S189.

Liu, J. J.; Yang, Y.; Zhu, W. W.; Yi, X.; Dong, Z. L.; Xu, X. N.; Chen, M. W.; Yang, K.; Lu, G.; Jiang, L. X. et al. Nanoscale metal– organic frameworks for combined photodynamic & radiation therapy in cancer treatment. Biomaterials 2016, 97, 1–9.

Maggiorella, L.; Barouch, G.; Devaux, C.; Pottier, A.; Deutsch, E.; Bourhis, J.; Borghi, E.; Levy, L. Nanoscale radiotherapy with hafnium oxide nanoparticles. Future Oncol. 2012, 8, 1167–1181.

Marill, J.; Anesary, N. M.; Zhang, P.; Vivet, S.; Borghi, E.; Levy, L.; Pottier, A. Hafnium oxide nanoparticles: Toward an in vitro predictive biological effect? Radiat. Oncol. 2014, 9, 150.

McGinnity, T. L.; Dominguez, O.; Curtis, T. E.; Nallathamby, P. D.; Hoffman, A. J.; Roeder, R. K. Hafnia (HfO₂) nanoparticles as an X-ray contrast agent and mid-infrared biosensor. Nanoscale 2016, 8, 13627–13637.

Li, Y. Y.; Qi, Y. C.; Zhang, H. B.; Xia, Z. M.; Xie, T. T.; Li, W. L.; Zhong, D. N.; Zhu, H. L.; Zhou, M. Gram-scale synthesis of highly biocompatible and intravenous injectable hafnium oxide nanocrystal with enhanced radiotherapy efficacy for cancer theranostic. Biomaterials 2020, 226, 119538.

Ramadoss, A.; Krishnamoorthy, K.; Kim, S. J. Novel synthesis of hafnium oxide nanoparticles by precipitation method and its characterization. Mater. Res. Bull. 2012, 47, 2680–2684.

Detappe, A.; Lux, F.; Tillement, O. Pushing radiation therapy limitations with theranostic nanoparticles. Nanomedicine 2016, 11, 997–999.

Havron, A.; Davis, M. A.; Selter, S. E.; Paskins-Hurlburt, A. J.; Hessel, S. J. Heavy metal particulate contrast materials for computed tomography of the liver. J. Comput. Assist. Tomogr. 1980, 4, 642–648.

Verry, C.; Sancey, L.; Dufort, S.; Le Duc, G.; Mendoza, C.; Lux, F.; Grand, S.; Arnaud, J.; Quesada, J. L.; Villa, J. et al. Treatment of multiple brain metastases using gadolinium nanoparticles and radiotherapy: Nano-rad, a phase I study protocol. BMJ. Open. 2019, 9, e023591.

Sancey, L.; Kotb, S.; Truillet, C.; Appaix, F.; Marais, A.; Thomas, E.; van der Sanden, B.; Klein, J. P.; Laurent, B.; Cottier, M. et al. Long-term in vivo clearance of gadolinium-based AGuIX nanoparticles and their biocompatibility after systemic injection. ACS Nano 2015, 9, 2477–2488.

Mowat, P.; Mignot, A.; Rima, W.; Lux, F.; Tillement, O.; Roulin, C.; Dutreix, M.; Bechet, D.; Huger, S.; Humbert, L. et al. In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells. J. Nanosci. Nanotechnol. 2011, 11, 7833–7839.

Miladi, I.; Aloy, M. T.; Armandy, E.; Mowat, P.; Kryza, D.; Magne, N.; Tillement, O.; Lux, F.; Billotey, C.; Janier, M. et al. Combining ultrasmall gadolinium-based nanoparticles with photon irradiation overcomes radioresistance of head and neck squamous cell carcinoma. Nanomedicine 2015, 11, 247–257.

Luchette, M.; Korideck, H.; Makrigiorgos, M.; Tillement, O.; Berbeco, R. Radiation dose enhancement of gadolinium-based aguix nanoparticles on hela cells. Nanomedicine 2014, 10, 1751–1755.

Kotb, S.; Detappe, A.; Lux, F.; Appaix, F.; Barbier, E. L.; Tran, V. L.; Plissonneau, M.; Gehan, H.; Lefranc, F.; Rodriguez-Lafrasse, C. et al. Gadolinium-based nanoparticles and radiation therapy for multiple brain melanoma metastases: Proof of concept before phase I trial. Theranostics 2016, 6, 418–427.

Detappe, A.; Kunjachan, S.; Sancey, L.; Motto-Ros, V.; Biancur, D.; Drane, P.; Guieze, R.; Makrigiorgos, G. M.; Tillement, O.; Langer, R. et al. Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy. J. Control. Release 2016, 238, 103–113.

Yong, Y.; Zhang, C. F.; Gu, Z. J.; Du, J. F.; Guo, Z.; Dong, X. H.; Xie, J. N.; Zhang, G. J.; Liu, X. F.; Zhao, Y. L. Polyoxometalate-based radiosensitization platform for treating hypoxic tumors by attenuating radioresistance and enhancing radiation response. ACS Nano 2017, 11, 7164–7176.

Brown, R.; Tehei, M.; Oktaria, S.; Briggs, A.; Stewart, C.; Konstantinov, K.; Rosenfeld, A.; Corde, S.; Lerch, M. High-Z nanostructured ceramics in radiotherapy: First evidence of Ta₂O₅-induced dose enhancement on radioresistant cancer cells in an MV photon field. Part. Part. Syst. Charact. . 2014, 31, 500–505.

McKinnon, S.; Engels, E.; Tehei, M.; Konstantinov, K.; Corde, S.; Oktaria, S.; Incerti, S.; Lerch, M.; Rosenfeld, A.; Guatelli, S. Study of the effect of ceramic Ta₂O₅ nanoparticle distribution on cellular dose enhancement in a kilovoltage photon field. Phys. Med. 2016, 32, 1216–1224.

Engels, E.; Corde, S.; McKinnon, S.; Incerti, S.; Konstantinov, K.; Rosenfeld, A.; Tehei, M.; Lerch, M.; Guatelli, S. Optimizing dose enhancement with Ta₂O₅ nanoparticles for synchrotron microbeam activated radiation therapy. Phys. Med. 2016, 32, 1852–1861.

Song, G. S.; Chen, Y. Y.; Liang, C.; Yi, X.; Liu, J. J.; Sun, X. Q.; Shen, S. D.; Yang, K.; Liu, Z. Catalase-loaded TaO_x nanoshells as bio-nanoreactors combining high-Z element and enzyme delivery for enhancing radiotherapy. Adv. Mater. 2016, 28, 7143–7148.

Song, G. S.; Chao, Y.; Chen, Y. Y.; Liang, C.; Yi, X.; Yang, G. B.; Yang, K.; Cheng, L.; Zhang, Q.; Liu, Z. All-in-one theranostic nanoplatform based on hollow TaO_x for chelator-free labeling imaging, drug delivery, and synergistically enhanced radiotherapy. Adv. Funct. Mater. 2016, 26, 8243–8254.

Chen, Y. Y.; Song, G. S.; Dong, Z. L.; Yi, X.; Chao, Y.; Liang, C.; Yang, K.; Cheng, L.; Liu, Z. Drug-loaded mesoporous tantalum oxide nanoparticles for enhanced synergetic chemoradiotherapy with reduced systemic toxicity. Small 2017, 13, 1602869.

Song, G. S.; Ji, C. H.; Liang, C.; Song, X. J.; Yi, X.; Dong, Z. L.; Yang, K.; Liu, Z. TaO_x decorated perfluorocarbon nanodroplets as oxygen reservoirs to overcome tumor hypoxia and enhance cancer radiotherapy. Biomaterials 2017, 112, 257–263.

He, W. Y.; Ai, K. L.; Lu, L. H. Nanoparticulate X-ray CT contrast agents. Sci. China Chem. 2015, 58, 753–760.

Yu, S. B.; Droege, M.; Segal, B.; Kim, S. H.; Sanderson, T.; Watson, A. D. Cuboidal W₃S₄ cluster complexes as new generation X-ray contrast agents. Inorg. Chem. 2000, 39, 1325–1328.

Firouzi, M.; Poursalehi, R.; Delavari, H. H.; Saba, F.; Oghabian, M. A. Chitosan coated tungsten trioxide nanoparticles as a contrast agent for X-ray computed tomography. Int. J. Biol. Macromol. 2017, 98, 479–485.

Jakhmola, A.; Anton, N.; Anton, H.; Messaddeq, N.; Hallouard, F.; Klymchenko, A.; Mely, Y.; Vandamme, T. F. Poly-ε -caprolactone tungsten oxide nanoparticles as a contrast agent for X-ray computed tomography. Biomaterials 2014, 35, 2981–2986.

Kim, S. J.; Xu, W. L.; Ahmad, M. W.; Baeck, J. S.; Chang, Y. M.; Bae, J. E.; Chae, K. S.; Kim, T. J.; Park, J. A.; Lee, G. H. Synthesis of nanoparticle CT contrast agents: In vitro and in vivo studies. Sci. Technol. Adv. Mat. 2015, 16, 055003.

Cheng, L.; Yuan, C.; Shen, S. D.; Yi, X.; Gong, H.; Yang, K.; Liu, Z. Bottom-up synthesis of metal-ion-doped WS₂ nanoflakes for cancer theranostics. ACS Nano 2015, 9, 11090–11101.

Wen, L.; Chen, L.; Zheng, S. M.; Zeng, J. F.; Duan, G. X.; Wang, Y.; Wang, G. L.; Chai, Z. F.; Li, Z.; Gao, M. Y. Ultrasmall biocompatible WO_3–x nanodots for multi-modality imaging and combined therapy of cancers. Adv. Mater. 2016, 28, 5072–5079.

Qiu, J. J.; Xiao, Q. F.; Zheng, X. P.; Zhang, L. B.; Xing, H. Y.; Ni, D. L.; Liu, Y. Y.; Zhang, S. J.; Ren, Q. G.; Hua, Y. Q. et al. Single W₁₈O₄₉ nanowires: A multifunctional nanoplatform for computed tomography imaging and photothermal/photodynamic/radiation synergistic cancer therapy. Nano Res. 2015, 8, 3580–3590.

Yong, Y.; Cheng, X. J.; Bao, T.; Zu, M.; Yan, L.; Yin, W. Y.; Ge, C. C.; Wang, D. L.; Gu, Z. J.; Zhao, Y. L. Tungsten sulfide quantum dots as multifunctional nanotheranostics for in vivo dual-modal image-guided photothermal/radiotherapy synergistic therapy. ACS Nano 2015, 9, 12451–12463.

Yong, Y.; Zhou, L. J.; Zhang, S. S.; Yan, L.; Gu, Z. J.; Zhang, G. J.; Zhao, Y. L. Gadolinium polytungstate nanoclusters: A new theranostic with ultrasmall size and versatile properties for dual-modal MR/CT imaging and photothermal therapy/radiotherapy of cancer. NPG Asia Mater. 2016, 8, e273.

Porcel, E.; Liehn, S.; Remita, H.; Usami, N.; Kobayashi, K.; Furusawa, Y.; Le Sech, C.; Lacombe, S. Platinum nanoparticles: A promising material for future cancer therapy? Nanotechnology 2010, 21, 085103.

K. A, M. A.; Rashid, R. A.; Lazim, R. M.; Dollah, N.; Razak, K. A.; Rahman, W. N. Evaluation of radiosensitization effects by platinum nanodendrites for 6 mv photon beam radiotherapy. Radiat. Phys. Chem. 2018, 150, 40–45.

Yao, M. H.; Ma, M.; Chen, Y.; Jia, X. Q.; Xu, G.; Xu, H. X.; Chen, H. R.; Wu, R. Multifunctional Bi₂S₃/PLGA nanocapsule for combined HIFU/radiation therapy. Biomaterials 2014, 35, 8197–8205.

Ebel, H.; Svagera, R.; Ebel, M. F.; Shaltout, A.; Hubbell, J. H. Numerical description of photoelectric absorption coefficients for fundamental parameter programs. X-Ray Spectrom. 2003, 32, 442–451.

Yokoya, A.; Shikazono, N.; Fujii, K.; Urushibara, A.; Akamatsu, K.; Watanabe, R. DNA damage induced by the direct effect of radiation. Radiat. Phys. Chem. 2008, 77, 1280–1285.

Tominaga, H.; Kodama, S.; Matsuda, N.; Suzuki, K.; Watanabe, M. Involvement of reactive oxygen species (ROS) in the induction of genetic instability by radiation. J. Radiat. Res. 2004, 45, 181–188.

Karnas, S. J.; Moiseenko, V. V.; Yu, E.; Truong, P.; Battista, J. J. Monte carlo simulations and measurement of DNA damage from X-ray-triggered auger cascades in iododeoxyuridine (IUdR). Radiat. Environ. Biophys. 2001, 40, 199–206.

Chompoosor, A.; Saha, K.; Ghosh, P. S.; Macarthy, D. J.; Miranda, O. R.; Zhu, Z. J.; Arcaro, K. F.; Rotello, V. M. The role of surface functionality on acute cytotoxicity, ROS generation and DNA damage by cationic gold nanoparticles. Small 2010, 6, 2246–2249.

Zhang, X. D.; Wu, D.; Shen, X.; Chen, J.; Sun, Y. M.; Liu, P. X.; Liang, X. J. Size-dependent radiosensitization of PEG-coated gold nanoparticles for cancer radiation therapy. Biomaterials 2012, 33, 6408–6419.

Jiang, W.; Li, Q.; Xiao, L.; Dou, J. X.; Liu, Y.; Yu, W. H.; Ma, Y. C.; Li, X. Q.; You, Y. Z.; Tong, Z. T. et al. Hierarchical multiplexing nanodroplets for imaging-guided cancer radiotherapy via DNA damage enhancement and concomitant DNA repair prevention. ACS Nano 2018, 12, 5684–5698.

Borran, A. A.; Aghanejad, A.; Farajollahi, A.; Barar, J.; Omidi, Y. Gold nanoparticles for radiosensitizing and imaging of cancer cells. Radiat. Phys. Chem. 2018, 152, 137–144.

Amendola, V.; Pilot, R.; Frasconi, M.; Maragò, O. M.; Iati, M. A. Surface plasmon resonance in gold nanoparticles: A review. J. Phys. : Condens. Matter. 2017, 29, 203002.

Choi, W. I.; Sahu, A.; Kim, Y. H.; Tae, G. Photothermal cancer therapy and imaging based on gold nanorods. Ann. Biomed. Eng. 2012, 40, 534–546.

El-Sayed, I. H.; Huang, X. H.; El-Sayed, M. A. Surface plasmon resonance scattering and absorption of anti-EGFR antibody conjugated gold nanoparticles in cancer diagnostics: Applications in oral cancer. Nano Lett. 2005, 5, 829–834.

Li, R.; Feng, F.; Chen, Z. Z.; Bai, Y. F.; Guo, F. F.; Wu, F. Y.; Zhou, G. Sensitive detection of carcinoembryonic antigen using surface plasmon resonance biosensor with gold nanoparticles signal amplification. Talanta 2015, 140, 143–149.

Gnedenko, O. V.; Mezentsev, Y. V.; Molnar, A. A.; Lisitsa, A. V.; Ivanov, A. S.; Archakov, A. I. Highly sensitive detection of human cardiac myoglobin using a reverse sandwich immunoassay with a gold nanoparticle-enhanced surface plasmon resonance biosensor. Anal. Chim. Acta. 2013, 759, 105–109.

Huang, X. H.; El-Sayed, I. H.; Qian, W.; El-Sayed, M. A. Cancer cells assemble and align gold nanorods conjugated to antibodies to produce highly enhanced, sharp, and polarized surface raman spectra: A potential cancer diagnostic marker. Nano Lett. 2007, 7, 1591– 1597.

Yang, X.; Yang, M. X.; Pang, B.; Vara, M.; Xia, Y. N. Gold nanomaterials at work in biomedicine. Chem. Rev. 2015, 115, 10410–10488.

Chen, N.; Yang, W. T.; Bao, Y.; Xu, H. L.; Qin, S. B.; Tu, Y. BSA capped Au nanoparticle as an efficient sensitizer for glioblastoma tumor radiation therapy. RSC Adv. 2015, 5, 40514–40520.

Chang, M. Y.; Shiau, A. L.; Chen, Y. H.; Chang, C. J.; Chen, H. H. W.; Wu, C. L. Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice. Cancer Sci. 2008, 99, 1479–1484.

Dorsey, J. F.; Sun, L.; Joh, D. Y.; Witztum, A.; Kao, G. D.; Alonso-Basanta, M.; Avery, S.; Hahn, S. M.; Al Zaki, A.; Tsourkas, A. Gold nanoparticles in radiation research: Potential applications for imaging and radiosensitization. Transl. Cancer Res. 2013, 2, 280–291.

Kandanapitiye, M. S.; Gao, M.; Molter, J.; Flask, C. A.; Huang, S. D. Synthesis, characterization, and X-ray attenuation properties of ultrasmall bioi nanoparticles: Toward renal clearable particulate CT contrast agents. Inorg. Chem. 2014, 53, 10189–10194.

Li, Z. L.; Hu, Y.; Howard, K. A.; Jiang, T. T.; Fan, X. L.; Miao, Z. H.; Sun, Y.; Besenbacher, F.; Yu, M. Multifunctional bismuth selenide nanocomposites for antitumor thermo-chemotherapy and imaging. ACS Nano 2016, 10, 984–997.

Mao, F. X.; Wen, L.; Sun, C. X.; Zhang, S. H.; Wang, G. L.; Zeng, J. F.; Wang, Y.; Ma, J. M.; Gao, M. Y.; Li, Z. Ultrasmall biocompatible Bi₂Se₃ nanodots for multimodal imaging-guided synergistic radiophotothermal therapy against cancer. ACS Nano 2016, 10, 11145–11155.

Song, G. S.; Liang, C.; Yi, X.; Zhao, Q.; Cheng, L.; Yang, K.; Liu, Z. A. Perfluorocarbon-loaded hollow Bi₂Se₃ nanoparticles for timely supply of oxygen under near-infrared light to enhance the radiotherapy of cancer. Adv. Mater. 2016, 28, 2716–2723.

Li, J.; Jiang, F.; Yang, B.; Song, X. R.; Liu, Y.; Yang, H. H.; Cao, D. R.; Shi, W. R.; Chen, G. N. Topological insulator bismuth selenide as a theranostic platform for simultaneous cancer imaging and therapy. Sci. Rep. 2013, 3, 1998.

Lei, P. P.; An, R.; Zhang, P.; Yao, S.; Song, S. Y.; Dong, L. L.; Xu, X.; Du, K. M.; Feng, J.; Zhang, H. Ultrafast synthesis of ultrasmall poly(vinylpyrrolidone)-protected bismuth nanodots as a multifunctional theranostic agent for in vivo dual-modal CT/photothermal-imaging-guided photothermal therapy. Adv. Funct. Mater. 2017, 27, 1702018.

Rathnayake, S.; Mongan, J.; Torres, A. S.; Colborn, R.; Gao, D. W.; Yeh, B. M.; Fu, Y. J. In vivo comparison of tantalum, tungsten, and bismuth enteric contrast agents to complement intravenous iodine for double-contrast dual-energy CT of the bowel. Contrast Media Mol. Imaging 2016, 11, 254–261.

Deng, J. J.; Xu, S. D.; Hu, W. K.; Xun, X. J.; Zheng, L. Y.; Su, M. Tumor targeted, stealthy and degradable bismuth nanoparticles for enhanced X-ray radiation therapy of breast cancer. Biomaterials 2018, 154, 24–33.

Jiao, L.; Li, Q. X.; Deng, J. J.; Okosi, N.; Xia, J. F.; Su, M. Nanocellulose templated growth of ultra-small bismuth nanoparticles for enhanced radiation therapy. Nanoscale 2018, 10, 6751–6757.

Colon, J.; Herrera, L.; Smith, J.; Patil, S.; Komanski, C.; Kupelian, P.; Seal, S.; Jenkins, D. W.; Baker, C. H. Protection from radiation-induced pneumonitis using cerium oxide nanoparticles. Nanomedicine 2009, 5, 225–231.

Nair, L. S.; Laurencin, C. T. Silver nanoparticles: Synthesis and therapeutic applications. J. Biomed. Nanotechnol. 2007, 3, 301–316.

McQuade, C.; Al Zaki, A.; Desai, Y.; Vido, M.; Sakhuja, T.; Cheng, Z. L.; Hickey, R. J.; Joh, D.; Park, S. J.; Kao, G. et al. A multifunctional nanoplatform for imaging, radiotherapy, and the prediction of therapeutic response. Small 2015, 11, 834–843.

Ni, K. Y.; Lan, G. X.; Chan, C.; Quigley, B.; Lu, K. D.; Aung, T.; Guo, N. N.; La Riviere, P.; Weichselbaum, R. R.; Lin, W. B. Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy. Nat. Commun. 2018, 9, 2351.

Mendoza, J. G.; Frutis, M. A. A.; Flores, G. A.; Hipólito, M. G.; Maciel Cerda, A.; Azorín Nieto, J.; Montalvo, T. R.; Falcony, C. Synthesis and characterization of hafnium oxide films for thermo and photoluminescence applications. Appl. Radiat. Isot. 2010, 68, 696–699.

Bonvalot, S.; Le Pechoux, C.; De Baere, T.; Kantor, G.; Buy, X.; Stoeckle, E.; Terrier, P.; Sargos, P.; Coindre, J. M.; Lassau, N. et al. First-in-human study testing a new radioenhancer using nanoparticles (NBTXR3) activated by radiation therapy in patients with locally advanced soft tissue sarcomas. Clin. Cancer Res. 2017, 23, 908–917.

Pracht, M.; Chajon, E.; de Baere, T.; Nguyen, F.; Bronowicki, J. P.; Vendrely, V.; Baumann, A. S.; Croise-Laurent, V.; Rio, E.; Rolland, Y. et al. Hepatocellular carcinoma and liver metastasis treated by hafnium oxide nanoparticles activated by stereotactic body radiation therapy. Ann. Oncol. 2018, 29, viii240.

Pottier, A.; Borghi, E.; Levy, L. Metals as radio-enhancers in oncology: The industry perspective. Biochem. Biophys. Res. Commun. 2015, 468, 471–475.

Pottier, A.; Borghi, E.; Levy, L. New use of metals as nanosized radioenhancers. Anticancer Res. 2014, 34, 443–453.

Kotagiri, N.; Sudlow, G. P.; Akers, W. J.; Achilefu, S. Breaking the depth dependency of phototherapy with cerenkov radiation and low-radiance-responsive nanophotosensitizers. Nat. Nanotechnol. 2015, 10, 370–379.

Alric, C.; Miladi, I.; Kryza, D.; Taleb, J.; Lux, F.; Bazzi, R.; Billotey, C.; Janier, M.; Perriat, P.; Roux, S. et al. The biodistribution of gold nanoparticles designed for renal clearance. Nanoscale 2013, 5, 5930–5939.

Barreto, J. A.; O'Malley, W.; Kubeil, M.; Graham, B.; Stephan, H.; Spiccia, L. Nanomaterials: Applications in cancer imaging and therapy. Adv. Mater. 2011, 23, H18–H40.

Longmire, M.; Choyke, P. L.; Kobayashi, H. Clearance properties of nano-sized particles and molecules as imaging agents: Considerations and caveats. Nanomedicine 2008, 3, 703–717.

Zhao, Y.; Peng, J.; Li, J. L.; Huang, L.; Yang, J. Y.; Huang, K.; Li, H. W.; Jiang, N.; Zheng, S. K.; Zhang, X. N. et al. Tumor-targeted and clearable human protein-based mri nanoprobes. Nano Lett. 2017, 17, 4096–4100.

Yu, M. X.; Zheng, J. Clearance pathways and tumor targeting of imaging nanoparticles. ACS Nano 2015, 9, 6655–6674.

Zhang, X. D.; Wu, D.; Shen, X.; Liu, P. X.; Fan, F. Y.; Fan, S. J. In vivo renal clearance, biodistribution, toxicity of gold nanoclusters. Biomaterials 2012, 33, 4628–4638.