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Defect-rich titanium nitride nanoparticle with high microwave-acoustic conversion efficiency for thermoacoustic imaging-guided deep tumor therapy

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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.

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References

  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.

    Google Scholar 

  2. Fessler, J. L.; Gajewski, T. F. The microbiota: A new variable impacting cancer treatment outcomes. Clin. Cancer Res. 2017, 23, 3229–3231.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  8. Cheng, L.; Wang, C.; Feng, L. Z.; Yang, K.; Liu, Z. Functional nanomaterials for phototherapies of cancer. Chem. Rev. 2014, 114, 10869–10939.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  14. Dolmans, D. E. J. G. J.; Fukumura, D.; Jain, R. K. Photodynamic therapy for cancer. Nat. Rev. Cancer. 2003, 3, 380–387.

    Article  CAS  Google Scholar 

  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.

    Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  23. Zhou, F. F.; Wu, S. N.; Yuan, Y.; Chen, W. R.; Xing, D. Mitochondriatargeting photoacoustic therapy using single-walled carbon nanotubes. Small 2012, 8, 1543–1550.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  34. He, Y.; Shen, Y. C.; Liu, C. J.; Wang, L. V. Suppressing excitation effects in microwave induced thermoacoustic tomography by multiview Hilbert transformation. Appl. Phys. Lett. 2017, 110, 053701.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  39. Ishii, S.; Sugavaneshwar, R. P.; Nagao, T. Titanium nitride nanoparticles as plasmonic solar heat transducers. J. Phys. Chem. C 2016, 120, 2343–2348.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  44. Deng, L. J.; Han, M. G. Microwave absorbing performances of multiwalled carbon nanotube composites with negative permeability. Appl. Phys. Lett. 2007, 91, 023119.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

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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).

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Authors and Affiliations

  1. MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China

    Zhujun Wu, Fanchu Zeng, Le Zhang, Shuxiang Zhao, Linghua Wu, Huan Qin & Da Xing

  2. Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China

    Zhujun Wu, Fanchu Zeng, Le Zhang, Shuxiang Zhao, Linghua Wu, Huan Qin & Da Xing

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  1. Zhujun Wu
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  2. Fanchu Zeng
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  3. Le Zhang
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  5. Linghua Wu
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  6. Huan Qin
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Correspondence to Huan Qin or Da Xing.

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Defect-rich titanium nitride nanoparticle with high microwaveacoustic conversion efficiency for thermoacoustic imaging-guided deep tumor therapy

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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 Res. 14, 2717–2727 (2021). https://doi.org/10.1007/s12274-020-3277-8

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