Research Article
Issue
Published:
29 December 2020
Defect-rich titanium nitride nanoparticle with high microwave-acoustic conversion efficiency for thermoacoustic imaging-guided deep tumor therapy
Keywords:
defect-rich titanium nitride nanoparticles, pulse microwave excited thermoacoustic therapy, thermoacoustic imaging, mitochondria-targeting, deep-seated tumor model
Cite this article:
Wu Z, Zeng F, Zhang L, et al.
Defect-rich titanium nitride nanoparticle with high microwave-acoustic conversion efficiency for thermoacoustic imaging-guided deep tumor therapy.
Nano Research,
2021, 14(8): 2717-2727.
https://doi.org/10.1007/s12274-020-3277-8
Download citation
545
Views
18
Downloads
Citations
13
Crossref
N/A
WoS
13
Scopus
3
CSCD
Pulse microwave excite thermoacoustic (TA) shockwave to destroy tumor cells in situ. This has promising applications for precise tumor therapy in deep tissue. Nanoparticle (NP) with high microwave-acoustic conversion is the key to enhance the efficiency of therapy. In this study, we firstly developed defect-rich titanium nitride nanoparticles (TiN NPs) for pulse microwave excited thermoacoustic (MTA) therapy. Due to a large number of local structural defects and charge carriers, TiN NPs exhibit excellent electromagnetic absorption through the dual mechanisms of dielectric loss and resistive loss. With pulsed microwave irradiation, it efficiently converts the microwave energy into shockwave via thermocavitation effect, achieving localized mechanical damage of mitochondria in the tumor cell and yielding a precise antitumor effect. In addition to the therapeutic function, the NP-mediated TA process also generates images that provide valuable information, including tumor size, shape, and location for treatment planning and monitoring. The experimental results showed that the TiN NPs could be efficiently accumulated in the tumor via intravenous infusion. With the deep tissue penetration characteristics of microwave, the proposed TiN-mediated MTA therapy effectively and precisely cures tumors in deep tissue without any detectable side effects. The results indicated that defect-rich TiN NPs are promising candidates for tumor therapy.
menu
Abstract
Full text
Outline
Electronic supplementary material
About this article
Defect-rich titanium nitride nanoparticle with high microwave-acoustic conversion efficiency for thermoacoustic imaging-guided deep tumor therapy
Abstract
Pulse microwave excite thermoacoustic (TA) shockwave to destroy tumor cells in situ. This has promising applications for precise tumor therapy in deep tissue. Nanoparticle (NP) with high microwave-acoustic conversion is the key to enhance the efficiency of therapy. In this study, we firstly developed defect-rich titanium nitride nanoparticles (TiN NPs) for pulse microwave excited thermoacoustic (MTA) therapy. Due to a large number of local structural defects and charge carriers, TiN NPs exhibit excellent electromagnetic absorption through the dual mechanisms of dielectric loss and resistive loss. With pulsed microwave irradiation, it efficiently converts the microwave energy into shockwave via thermocavitation effect, achieving localized mechanical damage of mitochondria in the tumor cell and yielding a precise antitumor effect. In addition to the therapeutic function, the NP-mediated TA process also generates images that provide valuable information, including tumor size, shape, and location for treatment planning and monitoring. The experimental results showed that the TiN NPs could be efficiently accumulated in the tumor via intravenous infusion. With the deep tissue penetration characteristics of microwave, the proposed TiN-mediated MTA therapy effectively and precisely cures tumors in deep tissue without any detectable side effects. The results indicated that defect-rich TiN NPs are promising candidates for tumor therapy.
Keywords:
defect-rich titanium nitride nanoparticles, pulse microwave excited thermoacoustic therapy, thermoacoustic imaging, mitochondria-targeting, deep-seated tumor model
References(59)
[1]
Miller, K. D.; Siegel, R. L.; Lin, C. C.; Mariotto, A. B.; Kramer, J. L.; Rowland, J. H.; Stein, K. D.; Alteri, R.; Jemal, A. Cancer treatment and survivorship statistics, 2016. CA: Cancer J. Clin. 2016, 66, 271-289.
[2]
Fessler, J. L.; Gajewski, T. F. The microbiota: A new variable impacting cancer treatment outcomes. Clin. Cancer Res. 2017, 23, 3229-3231.
[3]
Colleoni, M.; Nole, F.; Minchella, I.; Noberasco, C.; Luini, A.; Orecchia, A.; Veronesi, P.; Zurrida, S.; Viale, G.; Goldhirsch, A. Pre-operative chemotherapy and radiotherapy in breast cancer. Eur. J. Cancer 1998, 34, 641-645.
[4]
Seib, F. P.; Pritchard, E. M.; Kaplan, D. L. Self-assembling doxorubicin silk hydrogels for the focal treatment of primary breast cancer. Adv. Funct. Mater. 2013, 23, 58-65.
[5]
Vélez-García, E.; Carpenter Jr, J. T.; Moore, M.; Vogel, C. L.; Marcial, V.; Ketcham, A.; Singh, K. P.; Bass, D.; Bartolucci, A. A.; Smalley, R. Postsurgical adjuvant chemotherapy with or without radiotherapy in women with breast cancer and positive axillary nodes: A South-Eastern Cancer Study Group (SEG) trial. Eur. J. Cancer 1992, 28, 1833-1837.
[6]
Blau, R.; Epshtein, Y.; Pisarevsky, E.; Tiram, G.; Dangoor, S. I.; Yeini, E.; Krivitsky, A.; Eldar-Boock, A; Ben-Shushan, D.; Gibori, H. et al. Image-guided surgery using near-infrared turn-on fluorescent nanoprobes for precise detection of tumor margins. Theranostics 2018, 8, 3437-3460.
[7]
Herskovic, A.; Martz, K.; Al-Sarraf, M.; Leichman, L.; Brindle, J.; Vaitkevicius, V.; Cooper, J.; Byhardt, R.; Davis, L.; Emami, B. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N. Engl. J. Med. 1992, 326, 1593-1598.
[8]
Cheng, L.; Wang, C.; Feng, L. Z.; Yang, K.; Liu, Z. Functional nanomaterials for phototherapies of cancer. Chem. Rev. 2014, 114, 10869-10939.
[9]
Liu, L. M.; Chen, Q.; Wen, L. W.; Li, C.; Qin, H.; Xing, D. Photoacoustic therapy for precise eradication of glioblastoma with a tumor site blood-brain barrier permeability upregulating nanoparticle. Adv. Funct. Mater. 2019, 29, 1808601.
[10]
Zhang, R.; Fan, X.; Meng, Z. Q.; Lin, H. P.; Jin, Q. T.; Gong, F.; Dong, Z. L.; Li, Y. Y.; Chen, Q.; Liu, Z. et al. Renal clearable Ru-based coordination polymer nanodots for photoacoustic imaging guided cancer therapy. Theranostics 2019, 9, 8266-8276.
[11]
Rong, P. F.; Yang, K.; Srivastan, A.; Kiesewetter, D. O.; Yue, X. Y.; Wang, F.; Nie, L. M.; Bhirde, A.; Wang, Z.; Liu, Z. et al. Photosensitizer loaded nano-graphene for multimodality imaging guided tumor photodynamic therapy. Theranostics 2014, 4, 229-239.
[12]
Shi, H. T.; Liu, T. L.; Fu, C. H.; Li, L. L.; Tan, L. F.; Wang, J. Z.; Ren, X. L.; Ren, J.; Wang, J. X.; Meng, X. W. Insights into a microwave susceptible agent for minimally invasive microwave tumor thermal therapy. Biomaterials 2015, 44, 91-102.
[13]
Wu, Q.; Li, M.; Tan, L. F.; Yu, J.; Chen, Z. Z.; Su, L. H.; Ren, X. L.; Fu, C. H.; Ren, J.; Li, L. F. et al. A tumor treatment strategy based on biodegradable BSA@ZIF-8 for simultaneously ablating tumors and inhibiting infection. Nanoscale Horiz. 2018, 3, 606-615.
[14]
Dolmans, D. E. J. G. J.; Fukumura, D.; Jain, R. K. Photodynamic therapy for cancer. Nat. Rev. Cancer. 2003, 3, 380-387.
[15]
Agostinis, P.; Berg, K.; Cengel, K. A.; Foster, T. H.; Girotti, A. W.; Gollnick, S. O.; Hahn, S. M.; Hamblin, M. R.; Juzeniene, A.; Kessel, D. et al. Golab, J. Photodynamic therapy of cancer: An update. CA: Cancer J. Clin. 2011, 61, 250-281.
[16]
Lyu, Y.; Zeng, J. F.; Jiang, Y. Y.; Zhen, X.; Wang, T.; Qiu, S. S.; Lou, X.; Gao, M. Y.; Pu, K. Y. Enhancing both biodegradability and efficacy of semiconducting polymer nanoparticles for photoacoustic imaging and photothermal therapy. ACS Nano 2018, 12, 1801-1810.
[17]
Yu, J.; Yang, C.; Li, J. D. S.; Ding, Y. C.; Zhang, L.; Yousaf, M. Z.; Lin, J.; Pang, R.; Wei, L. B.; Xu, L. L. et al. Multifunctional Fe5C2 nanoparticles: A targeted theranostic platform for magnetic resonance imaging and photoacoustic tomography-guided photothermal therapy. Adv. Mater. 2014, 26, 4114-4120.
[18]
Wang, Y.; Niu, G. L.; Zhai, S. D.; Zhang, W. J.; Xing, D. Specific photoacoustic cavitation through nucleus targeted nanoparticles for high-efficiency tumor therapy. Nano Res. 2020, 13, 719-728.
[19]
Krasovitski, B.; Frenkel, V.; Shoham, S.; Kimmel, E. Intramembrane cavitation as a unifying mechanism for ultrasound-induced bioeffects. Proc. Natl. Acad. Sci. USA 2011, 108, 3258-3263.
[20]
Shi, Y. J.; Qin, H.; Yang, S. H.; Xing, D. Thermally confined shell coating amplifies the photoacoustic conversion efficiency of nanoprobes. Nano Res. 2016, 9, 3644-3655.
[21]
Peeters, S.; Kitz, M.; Preisser, S.; Wetterwald, A.; Rothen-Rutishauser, B.; Thalmann, G. N.; Brandenberger, C.; Bailey, A.; Frenz, M. Mechanisms of nanoparticle-mediated photomechanical cell damage. Biomed. Opt. Express. 2012, 3, 435-446.
[22]
Qin, H.; Zhou, T.; Yang, S. H.; Xing, D. Fluorescence quenching nanoprobes dedicated to in vivo photoacoustic imaging and high-efficient tumor therapy in deep-seated tissue. Small 2015, 11, 2675-2686.
[23]
Zhou, F. F.; Wu, S. N.; Yuan, Y.; Chen, W. R.; Xing, D. Mitochondria-targeting photoacoustic therapy using single-walled carbon nanotubes. Small 2012, 8, 1543-1550.
[24]
Zhong, J. P.; Yang, S. H.; Zheng, X. H.; Zhou, T.; Xing, D. In vivo photoacoustic therapy with cancer-targeted indocyanine green-containing nanoparticles. Nanomedicine 2013, 8, 903-919.
[25]
Du, L. H.; Qin, H.; Ma, T.; Zhang, T.; Xing, D. In vivo imaging-guided photothermal/photoacoustic synergistic therapy with bioorthogonal metabolic glycoengineering-activated tumor targeting nanoparticles. ACS Nano 2017, 11, 8930-8943.
[26]
Lin, L. S.; Song, J. B.; Yang, H. H.; Chen, X. Y. Yolk-shell nanostructures: Design, synthesis, and biomedical applications. Adv. Mater. 2018, 30, 1704639.
[27]
Wang, Z. X.; Zhang, Y. M.; Cao, B.; Ji, Z.; Luo, W. L.; Zhai, S. D.; Zhang, D. D.; Wang, W. P.; Xing, D.; Hu, X. L. Explosible nanocapsules excited by pulsed microwaves for efficient thermoacoustic-chemo combination therapy. Nanoscale 2019, 11, 1710-1719.
[28]
Wen, L. W.; Yang, S. H.; Zhong, J. P.; Zhou, Q.; Xing, D. Thermoacoustic imaging and therapy guidance based on ultra-short pulsed microwave pumped thermoelastic effect induced with superparamagnetic iron oxide nanoparticles. Theranostics 2017, 7, 1976-1989.
[29]
Wen, L. W.; Ding, W. Z.; Yang, S. H.; Xing, D. Microwave pumped high-efficient thermoacoustic tumor therapy with single wall carbon nanotubes. Biomaterials 2016, 75, 163-173.
[30]
Zhai, S. D.; Hu, X. L.; Ji, Z.; Qin, H.; Wang, Z. X.; Hu, Y. J.; Xing, D. Pulsed microwave-pumped drug-free thermoacoustic therapy by highly biocompatible and safe metabolic polyarginine probes. Nano Lett. 2019, 19, 1728-1735.
[31]
Shi, H. T.; Nie, M.; Tan, L. F.; Liu, T. L.; Shao, H. B.; Fu, C. H.; Ren, X. L.; Ma, T. C.; Ren, J.; Li, L. L. et al. A smart all-in-one theranostic platform for CT imaging guided tumor microwave thermotherapy based on IL@ZrO2 nanoparticles. Chem. Sci. 2015, 6, 5016-5026.
[32]
Du, Q. J.; Fu, C. H.; Tie, J.; Liu, T. L.; Li, L. L.; Ren, X. L.; Huang, Z. B.; Liu, H. Y.; Tang, F. Q.; Li, L. et al. Gelatin microcapsules for enhanced microwave tumor hyperthermia. Nanoscale 2015, 7, 3147-3154.
[33]
Lou, C. G.; Yang, S. H.; Ji, Z.; Chen, Q.; Xing, D. Ultrashort microwave-induced thermoacoustic imaging: A breakthrough in excitation efficiency and spatial resolution. Phys. Rev. Lett. 2012, 109, 218101.
[34]
He, Y.; Shen, Y. C.; Liu, C. J.; Wang, L. V. Suppressing excitation effects in microwave induced thermoacoustic tomography by multi-view Hilbert transformation. Appl. Phys. Lett. 2017, 110, 053701.
[35]
Ding, W. Z.; Lou, C. G.; Qiu, J. S.; Zhao, Z. B.; Zhou, Q.; Liang, M. J.; Ji, Z.; Yang, S. H.; Xing, D. Targeted Fe-filled carbon nanotube as a multifunctional contrast agent for thermoacoustic and magnetic resonance imaging of tumor in living mice. Nanomedicine 2016, 12, 235-244.
[36]
Guler, U.; Ndukaife, J. C.; Naik, G. V.; Nnanna, A. G. A.; Kildishev, A. V.; Shalaev, V. M.; Boltasseva, A. Local heating with lithographically fabricated plasmonic titanium nitride nanoparticles. Nano Lett. 2013, 13, 6078-6083.
[37]
He, W. Y.; Ai, K. L.; Jiang, C. H.; Li, Y. Y.; Song, X. F.; Lu, L. H. Plasmonic titanium nitride nanoparticles for in vivo photoacoustic tomography imaging and photothermal cancer therapy. Biomaterials 2017, 132, 37-47.
[38]
Wang, C. M.; Dai, C.; Hu, Z. Q.; Li, H. Q.; Yu, L. D.; Lin, H.; Bai, J. W.; Chen, Y. Photonic cancer nanomedicine using the near infrared-II biowindow enabled by biocompatible titanium nitride nanoplatforms. Nanoscale Horiz. 2019, 4, 415-425.
[39]
Ishii, S.; Sugavaneshwar, R. P.; Nagao, T. Titanium nitride nanoparticles as plasmonic solar heat transducers. J. Phys. Chem. C 2016, 120, 2343-2348.
[40]
Li, W.; Guler, U.; Kinsey, N.; Naik, G. V.; Boltasseva, A.; Guan, J. G.; Shalaev, V. M.; Kildishev, A. V. Refractory plasmonics with titanium nitride: Broadband metamaterial absorber. Adv. Mater. 2014, 26, 7959-7965.
[41]
Guler, U.; Suslov, S.; Kildishev, A. V.; Boltasseva, A.; Shalaev, V. M. Colloidal plasmonic titanium nitride nanoparticles: Properties and applications. Nanophotonics 2015, 4, 269-276.
[42]
Liu, R.; Lun, N.; Qi, Y. X.; Bai, Y. J.; Zhu, H. L.; Han, F. D.; Meng, X. L.; Bi, J. Q.; Fan, R. H. Microwave absorption properties of TiN nanoparticles. J. Alloys Compd. 2011, 509, 10032-10035.
[43]
Morozov, I. G.; Belousova, O. V.; Belyakov, O. A.; Parkin, I. P.; Sathasivam, S.; Kuznetcov, M. V. Titanium nitride room-temperature ferromagnetic nanoparticles. J. Alloys Compd. 2016, 675, 266-276.
[44]
Deng, L. J.; Han, M. G. Microwave absorbing performances of multiwalled carbon nanotube composites with negative permeability. Appl. Phys. Lett. 2007, 91, 023119.
[45]
Watts, P. C. P.; Hsu, W. K.; Barnes, A.; Chambers, B. High permittivity from defective multiwalled carbon nanotubes in the X-band. Adv. Mater. 2003, 15, 600-603.
[46]
Li, Y. P.; Tan, Q. H.; Qin, H.; Xing, D. Defect-rich single-layer MoS2 nanosheets with high dielectric-loss for contrast-enhanced thermoacoustic imaging of breast tumor. Appl. Phys. Lett. 2019, 115, 073701.
[47]
Yuan, C.; Qin, B. H.; Qin, H.; Xing, D. Increasing dielectric loss of a graphene oxide nanoparticle to enhance the microwave thermoacoustic imaging contrast of breast tumor. Nanoscale 2019, 11, 22222-22229.
[48]
Kim, K. Y.; Jin, H. Y.; Park, J.; Jung, S. H.; Lee, J. H.; Park, H.; Kim, S. K.; Bae, J.; Jung, J. H. Mitochondria-targeting self-assembled nanoparticles derived from triphenylphosphonium-conjugated cyanostilbene enable site-specific imaging and anticancer drug delivery. Nano Res. 2018, 11, 1082-1098.
[49]
Tan, X.; Luo, S. L.; Long, L.; Wang, Y.; Wang, D. C.; Fang, S. T.; Qin, O. Y.; Su, Y. P.; Cheng, T. M.; Shi, C. M. Structure-guided design and synthesis of a mitochondria-targeting near-infrared fluorophore with multimodal therapeutic activities. Adv. Mater. 2017, 29, 1704196.
[50]
Noh, I.; Lee, D. Y.; Kim, H.; Jeong, C. U.; Lee, Y.; Ahn, J. O.; Hyun, H.; Park, J. H.; Kim, Y. C. Enhanced photodynamic cancer treatment by mitochondria-targeting and brominated near-infrared fluorophores. Adv. Sci. 2018, 5, 1700481.
[51]
Pan, R.; Liu, K. J.; Qi, Z. F. Zinc causes the death of hypoxic astrocytes by inducing ROS production through mitochondria dysfunction. Biophys. Rep. 2019, 5, 209-217.
[52]
Zhou, Y.; Kim, Y. S.; Yan, X.; Jacobson, O.; Chen, X. Y.; Liu, S. 64Cu-labeled lissamine rhodamine B: A promising PET radiotracer targeting tumor mitochondria. Mol. Pharm. 2011, 8, 1198-1208.
[53]
Xie, C.; Chang, J.; Hao, X. D.; Yu, J. M.; Liu, H. R.; Sun, X. Mitochondrial-targeted prodrug cancer therapy using a rhodamine B labeled fluorinated docetaxel. Eur. J. Pharm. Biopharm. 2013, 85, 541-549.
[54]
Chong, K. L.; Chalmers, B. A.; Cullen, J. K.; Kaur, A.; Kolanowski, J. L.; Morrow, B. J.; Fairfull-Smith, K. E.; Lavin, M. J.; Barnett, N. L.; New, E. J. et al. Pro-fluorescent mitochondria-targeted real-time responsive redox probes synthesised from carboxy isoindoline nitroxides: Sensitive probes of mitochondrial redox status in cells. Free Radic. Biol. Med. 2018, 128, 97-110.
[55]
Abbas, S. M.; Chandra, M.; Verma, A.; Chatterjee, R.; Goel, T. C. Complex permittivity and microwave absorption properties of a composite dielectric absorber. Compos. Part A Appl. Sci. Manuf. 2006, 37, 2148-2154.
[56]
Michielssen, E.; Sajer, J. M.; Ranjithan, S.; Mittra, R. Design of lightweight, broad-band microwave absorbers using genetic algorithms. IEEE Trans. Microw. Theory Tech. 1993, 41, 1024-1031.
[57]
Yu, X. L.; Yi, B.; Liu, F.; Wang, X. Y. Prediction of the dielectric dissipation factor tan δ of polymers with an ANN model based on the DFT calculation. React. Funct. Polym. 2008, 68, 1557-1562.
[58]
Nie, L. M.; Ou, Z. M.; Yang, S. H.; Xing, D. Thermoacoustic molecular tomography with magnetic nanoparticle contrast agents for targeted tumor detection. Med. Phys. 2010, 37, 4193-4200.
[59]
Fang, W.; Shi, Y. J.; Xing, D. Vacancy-defect-dipole amplifies the thermoacoustic conversion efficiency of carbon nanoprobes. Nano Res. 2020, 13, 2413-2419.
File
12274_2020_3277_MOESM1_ESM.pdf (4.3 MB)
Publication history
Copyright
Acknowledgements
Publication history
Received: 09 September 2020
Revised: 26 November 2020
Accepted: 02 December 2020
Published:
29 December 2020
Issue date: August 2021
Copyright
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020
Acknowledgements
This research was supported by the National Natural Science Foundation of China (No. 62075066); the Science and Technology Planning Project of Guangdong Province, China (Nos. 2019A1515012054); the Scientific and Technological Planning Project of Guangzhou City (No. 201805010002), and the Science and Technology Program of Guangzhou (No. 2019050001).
FEEDBACK 
TOP