Photodynamic therapy-induced precise attenuation of light-targeted semicircular canals for treating intractable vertigo

Abstract

Vertigo is a common symptom of various diseases that affects a large number of people worldwide. Current leading treatments for intractable peripheral vertigo are to intratympanically inject ototoxic drugs such as gentamicin to attenuate the semicircular canal function but inevitably cause hearing injury. Photodynamic therapy (PDT) is a noninvasive therapeutic approach by precisely targeting the diseased tissue. Here, we developed a PDT-based method for treating intractable peripheral vertigo in a mouse model using a polymer-coated photosensitizer chlorin e6 excited by red light. We found that a high dose of PDT attenuated the function of both semicircular canals and otolith organs and damaged their hair cells. Conversely, the PDT exerted no effect on hearing function or cochlear hair-cell viability. These results suggest the therapeutic potential of PDT for treating intractable peripheral vertigo without hurting hearing. Besides, the attenuation level and affected area can be precisely controlled by adjusting the light exposure time. Furthermore, we demonstrated the potential of this therapeutic approach to be minimally invasive with light irradiation through bone results. Thus, our PDT-based approach for attenuating the function of the semicircular canals offers a basis for developing a lessinvasive and targeted therapeutic option for treating vertigo.

Keywords

horizontal semicircular canal / intractable vertigo / photodynamic therapy / targeted therapy / vestibular apparatus

References

[1] H. K. Neuhauser, M. von Brevern, A. Radtke, F. Lezius, M. Feldmann, T. Ziese, T. Lempert, Neurology 2005, 65, 898.

[2] M. Strupp, M. Mandala, J. A. Lopez-Escamez, Curr. Opin. Neurol. 2019, 32, 165.

[3] D. E. Newman-Toker, Y. H. Hsieh, C. A. Camargo Jr., A. J. Pelletier, G. T. Butchy, J. A. Edlow, Mayo Clin. Proc. 2008, 83, 765.

[4] M. Strupp, T. Brandt, Dtsch Arztebl Int. 2008, 105, 173.

[5] K. A. Kerber, J. F. Burke, L. E. Skolarus, W. J. Meurer, B. C. Callaghan, D. L. Brown, L. D. Lisabeth, T. J. McLaughlin, A. M. Fendrick, L. B. Morgenstern, Otolaryngol. Head Neck Surg. 2013, 148, 425.

[6] G. J. Basura, M. E. Adams, A. Monfared, S. R. Schwartz, P. J. Antonelli, R. Burkard, M. L. Bush, J. Bykowski, M. Colandrea, J. Derebery, E. A. Kelly, K. A. Kerber, C. F. Koopman, A. A. Kuch, E. Marcolini, B. J. McKinnon, M. J. Ruckenstein, C. V. Valenzuela, A. Vosooney, S. A. Walsh, L. C. Nnacheta, N. Dhepyasuwan, E. M. Buchanan, Otolaryngol. Head Neck Surg. 2020, 162(S2), S1.

[7] L. H. Christopher, E. P. Wilkinson, Am. J. Otolaryngol. 2021, 42, 102817.

[8] F. Su, G. Li, J. Meng, Y. Gao, M. Cai, Q. Zhang, W. Meng, S. He, Front. Neurosci. 2022, 16, 977323.

[9] D. P. Schoo, B. M. Lin, Y. Agrawal, Oper. Tech. Otolaryngol. Head Neck Surg. 2021, 32, 99.

[10] Y. Chai, H. Li, in Meniere’s Disease (Ed: F. Bahmad, Jr) IntechOpen, 2020, Ch.5.

[11] J. Nevoux, M. Barbara, J. Dornhoffer, W. Gibson, T. Kitahara, V. Darrouzet, Eur. Ann. Otorhinolaryngol. Head Neck Dis. 2018, 135, S29.

[12] M. J. Manyak, A. Russo, P. D. Smith, E. Glatstein, J. Clin. Oncol. 1988, 6, 380.

[13] P. Agostinis, K. Berg, K. A. Cengel, T. H. Foster, A. W. Girotti, S. O. Gollnick, S. M. Hahn, M. R. Hamblin, A. Juzeniene, D. Kessel, M. Korbelik, J. Moan, P. Mroz, D. Nowis, J. Piette, B. C. Wilson, J. Golab, CA Cancer J. Clin. 2011, 61, 250.

[14] S. Kwiatkowski, B. Knap, D. Przystupski, J. Saczko, E. Kedzierska, K. Knap-Czop, J. Kotlinska, O. Michel, K. Kotowski, J. Kulbacka, Biomed. Pharmacother. 2018, 106, 1098.

[15] L. Chen, X. Wang, Y. Yuan, R. Hu, Q. Chen, L. Zhu, M. Gu, C. Shen, Eng. Regen. 2022, 3, 59.

[16] Y. Chen, H. Yu, Y. Zhang, W. Li, N. Lu, W. Ni, Y. He, J. Li, S. Sun, Z. Wang, H. Li, Sci. Rep. 2013, 3, 2996.

[17] W. Xiong, T. Wagner, L. Yan, N. Grillet, U. Muller, Nat. Protoc. 2014, 9, 2438.

[18] X. Yang, S. Zhou, J. Wu, Q. Liao, C. Wang, M. Liu, L. Qu, Y. Zhang, C. Cheng, R. Chai, K. Zhang, X. Yu, P. Huang, L. Liu, W. Xiong, S. Chen, F. Chen, Neurosci. Lett. 2019, 696, 212.

[19] Y. Zhang, S. Zhang, Z. Zhang, Y. Dong, X. Ma, R. Qiang, Y. Chen, X. Gao, C. Zhao, F. Chen, S. He, R. Chai, Aging 2020, 12, 19834.

[20] M. Beraneck, M. Bojados, A. Le Seac’h, M. Jamon, P. P. Vidal, PLoS One 2012, 7, e40414.

[21] K. Ono, J. Keller, O. L. Ramirez, A. G. Garrido, O. A. Zobeiri, H. H. V. Chang, S. Vijayakumar, A. Ayiotis, G. Duester, C. C. Della Santina, S. M. Jones, K. E. Cullen, R. A. Eatock, D. K. Wu, Nat. Commun. 2020, 11, 63.

[22] Y. Zhu, H. Jia, Z. Chen, F. Wu, Nanoscale 2017, 9, 12874.

[23] A. E. O’Connor, W. M. Gallagher, A. T. Byrne, Photochem. Photobiol. 2009, 85, 1053.

[24] M. F. Isaac-Lam, D. M. Hammonds, Pharmaceuticals 2017, 10, 41.

[25] X. Hu, H. Tian, W. Jiang, A. Song, Z. Li, Y. Luan, Small 2018, 14, 1802994.

[26] A. Akopov, G. Papayan, Photodiagn. Photodyn. Ther. 2021, 33, 102203.

[27] J. D. Spikes, J. C. Bommer, J. Photochem. Photobiol. B 1993, 17, 135.

[28] Y. Su, B. Zhang, R. Sun, W. Liu, Q. Zhu, X. Zhang, R. Wang, C. Chen, Drug Delivery 2021, 28, 1397.

[29] H. Cai, X. Wen, L. Wen, N. Tirelli, X. Zhang, Y. Zhang, H. Su, F. Yang, G. Chen, Int. J. Nanomed. 2014, 9, 5591.

[30] R. T. Horie, T. Sakamoto, T. Nakagawa, T. Ishihara, M. Higaki, J. Ito, Nanomedicine 2010, 5, 1331.

[31] H. Liu, P. Wu, S. Kuo, C. Chen, E. Chang, C. Wu, Y. Chan, J. Am. Chem. Soc. 2015, 137, 10420.

[32] Y. Yang, W. Hou, S. Liu, K. Sun, M. Li, C. Wu, Biomacromolecules 2018, 19, 201.

[33] J. Ma, J. Chen, M. Idowu, T. Nyokong, J. Phys. Chem. B 2008, 112, 4465.

[34] S. Tuncel, F. Dumoulin, J. Gailer, M. Sooriyaarachchi, D. Atilla, M. Durmus, D. Bouchu, H. Savoie, R. W. Boyle, V. Ahsen, Dalton Trans. 2011, 40, 4067.

[35] H. Shi, X. Ma, Q. Zhao, B. Liu, Q. Qu, Z. An, Y. Zhao, W. Huang, Adv. Funct. Mater. 2014, 24, 4823.

[36] N. Vanerio, M. Stijnen, B. de Mol, L. M. Kock, Photobiomodulation Photomed. Laser Surg. 2019, 37, 383.

[37] Y. Tang, H. Chen, K. Chang, Z. Liu, Y. Wang, S. Qu, H. Xu, C. Wu, ACS Appl. Mater. Interfaces 2017, 9, 3419.

[38] C. Harasztosi, E. Klenske, A. W. Gummer, Eur. J. Neurosci. 2021, 54, 4755.

[39] J. E. Gale, W. Marcotti, H. J. Kennedy, C. J. Kros, G. P. Richardson, J. Neurosci. 2001, 21, 7013.

[40] A. Ballesteros, T. S. Fitzgerald, K. J. Swartz, Hear. Res. 2021, 404, 108212.

[41] L. S. Parnes, S. K. Agrawal, J. Atlas, CMAJ 2003, 169, 681.

[42] S. Y. Moon, J. S. Kim, B. K. Kim, J. I. Kim, H. Lee, S. I. Son, K. S. Kim, C. K. Rhee, G. C. Han, W. S. Lee, J. Korean Med. Sci. 2006, 21, 539.

[43] K. P. Weber, S. M. Rosengren, R. Michels, V. Sturm, D. Straumann, K. Landau, J. Physiol. 2012, 590, 3091.

[44] T. Murofushi, K. Nishimura, M. Tsubota, Front. Neurol. 2022, 13, 872892.

[45] F. C. Timmer, G. Zhou, J. J. Guinan, S. G. Kujawa, B. S. Herrmann, S. D. Rauch, Laryngoscope 2006, 116, 776.

[46] H. Nakahara, E. Yoshimura, Y. Tsuda, T. Murofushi, Acta Otolaryngol. 2013, 133, 144.

[47] D. Zhang, Y. Lyu, Z. Fan, H. Wang, Laryngoscope 2023, 133, 1734.

[48] R. Wegmann-Vicuna, R. Manrique-Huarte, D. Calavia-Gil, E. Martin-Sanz, P. Marques, N. Perez-Fernandez, Front. Neurol. 2022, 13, 808570.

[49] O. R. Maarsingh, H. Stam, P. M. van de Ven, N. M. van Schoor, M. J. Ridd, J. C. van der Wouden, BMC Geriatr. 2014, 14, 133.

[50] Y. Agrawal, J. P. Carey, C. C. Della Santina, M. C. Schubert, L. B. Minor, Arch. Intern. Med. 2009, 169, 938.

[51] M. Karatas, Neurologist 2008, 14, 355.

[52] A. Scarpa, M. Ralli, E. De Bonis, D. Troisi, A. Montanino, P. Viola, G. Chiarella, F. M. Gioacchini, M. Cavaliere, E. Cassandro, C. Cassandro, Transl. Med. Unisa 2020, 23, 48.

[53] S. Li, I. Pyykko, Q. Zhang, J. Yang, M. Duan, Eur. Arch. Oto-Rhino-Laryngol. 2022, 279, 3795.

[54] S. Chin, Med. Hypotheses 2018, 116, 84.

[55] P. De Luca, M. Ralli, C. Cassandro, F. Y. Russo, F. M. Gioacchini, M. Cavaliere, M. Fiore, A. Greco, E. Cassandro, A. Scarpa, Int. Tinnitus J. 2022, 26, 50.

[56] P. You, R. Instrum, L. Parnes, Laryngoscope Investig. Otolaryngol. 2019, 4, 116.

[57] L. S. Parnes, J. A. McClure, Ann. Otol. Rhinol. Laryngol. 1990, 99, 330.

[58] S. Y. Lee, Y. S. Kim, B. Jeong, M. Carandang, J. W. Koo, S. H. Oh, J. H. Lee, Am. J. Otolaryngol. 2021, 42, 103086.

[59] W. Hao, H. Yu, H. Li, J. Neurol. 2022, 269, 72.

[60] Y. Guan, D. A. Chari, Y. H. Liu, S. D. Rauch, Front. Neurol. 2021, 12, 765208.

[61] K. D. Nguyen, L. B. Minor, C. C. Della Santina, J. P. Carey, Audiol. Neurotol. 2009, 14, 361.

[62] X. Xu, K. Xie, X. Zhang, E. M. Pridgen, G. Y. Park, D. S. Cui, J. Shi, J. Wu, P. W. Kantoff, S. J. Lippard, R. Langer, G. C. Walker, O. C. Farokhzad, Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 18638.

[63] X. An, D. Zha, Nanomedicine 2020, 15, 1981.

[64] D. C. Gheorghe, A. G. Niculescu, A. C. Birca, A. M. Grumezescu, Nanomaterials 2021, 11, 1311.

[65] B. Szeto, H. Chiang, C. Valentini, M. Yu, J. W. Kysar, A. K. Lalwani, Laryngoscope Investig. Otolaryngol. 2020, 5, 122.

[66] X. Wen, S. Ding, H. Cai, J. Wang, L. Wen, F. Yang, G. Chen, Int. J. Nanomed. 2016, 11, 5959.

[67] X. Ma, W. Zhou, R. Zhang, C. Zhang, J. Yan, J. Feng, J. M. Rosenholm, T. Shi, X. Shen, H. Zhang, Mater. Today Bio 2023, 20, 100663.

[68] J. A. Beyea, S. K. Agrawal, L. S. Parnes, Laryngoscope 2012, 122, 1862.

[69] R. M. Banakis Hartl, S. P. Cass, Otolaryngol. Head Neck Surg. 2018, 158, 534.

[70] R. Dundar, I. Iynen, A. Buyruk, Am. J. Otolaryngol. 2022, 43, 103242.

[71] B. Isaacson, J. B. Hunter, A. Rivas, Otolaryngol. Clin. N. Am. 2018, 51, 415.

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