Activation of mechanoluminescent nanotransducers by focused ultrasound enables light delivery to deep-seated tissue in vivo

Shan Jiang, Xiang Wu, Fan Yang, Nicholas J. Rommelfanger, Guosong Hong

Published: 2023-10-31 DOI: 10.1038/s41596-023-00895-8

mechanoluminescent nanotransducers

Extended

Extended Data Fig. 1

Representative TEM images of colloidal MLNTs of Sr 2 MgSi 2 O 7 :Eu,Dy, ZnS:Cu,Al, ZnS:Mn and CaTiO 3 :Pr. Figure reproduced with permission from ref. 22 , ACS.

Extended Data Fig. 2 Peak pressure measured by the hydrophone (black) plotted against the percent amplitude of the FUS system.

Linear fitting (black) yields an empirical formula: P = 0.1 A + 0.2, where P is the pressure in mega pascals and A is the amplitude in percent. Figure reproduced from ref. 20 . under the Creative Commons license CC BY 4.0 .

Extended Data Fig. 3

Pressure mapping of the 1.5-MHz FUS transducer in the x - y plane (at z 0 = 0) ( a ) and in the x - z plane (at y 0 = 0) ( b ).

Extended Data Fig. 4

Normalized mechanoluminescence spectra of MLNTs composed of Sr 2 MgSi 2 O 7 :Eu,Dy ( a ), ZnS:Cu,Al ( b ), ZnS:Mn ( c ) and CaTiO 3 :Pr ( d ). Figure adapted with permission from ref. 22 , ACS.

Extended Data Fig. 5

An example mechanoluminescence image ( a ) and its corresponding emission line profile fitted to a Gaussian function ( b ) to obtain the full-width-at-half-maximum (FWHM).

Extended Data Fig. 6

Representative rechargeability curves of MLNTs composed of Sr 2 MgSi 2 O 7 :Eu,Dy ( a ), ZnS:Cu,Al ( b ), ZnS:Mn ( c ) and CaTiO 3 :Pr ( d ). Figure reproduced with permission from ref. 22 , ACS.

Extended Data Fig. 7 Temporal kinetics of FUS-induced light emission from colloidal solutions of MLNTs.

a−d , Temporal kinetics of MLNT solutions composed of Sr 2 MgSi 2 O 7 :Eu,Dy ( a ), ZnS:Cu,Al ( b ), ZnS:Mn ( c ) and CaTiO 3 :Pr ( d ) upon 10-, 20- and 50-ms FUS pulses in the artificial circulatory system with an imaging frame rate of 200 Hz. e−h , Onset and offset times of mechanoluminescence emission measured from a–d . All data are presented as the mean ± s.d. of 10 independent measurements. ML, mechanoluminescence. Figure reproduced with permission from ref. 22 , ACS.

Extended Data Fig. 8

Emission intensity from mechanoluminescent fluids composed of Sr 2 MgSi 2 O 7 :Eu,Dy ( a ), ZnS:Cu,Al ( b ), ZnS:Mn ( c ) and CaTiO 3 :Pr ( d ) under varying FUS pressure. Figure reproduced with permission from ref. 22 , ACS.

Supplementary information

Reporting Summary

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High-quality and robust protein quantification in large clinical/pharmaceutical cohorts with IonStar proteomics investigation

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Experimental modulation of physiological force application on leg joint neurons in intactDrosophila melanogaster

Combining surface-accessible Ag and Au colloidal nanomaterials with SERS for in situ analysis of molecule–metal interactions in complex solution environments

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Kim, P. et al. In vivo wide-area cellular imaging by side-view endomicroscopy. Nat. Methods 7, 303–305 (2010).
Prominski, A. et al. Porosity-based heterojunctions enable leadless optoelectronic modulation of tissues. Nat. Mater. 21, 647–655 (2022).
Tian, B. Nongenetic neural control with light. Science 365, 457 (2019).
Xu, C. et al. Nanoparticles with ultrasound-induced afterglow luminescence for tumour-specific theranostics. Nat. Biomed. Eng. 7, 298–312 (2023).
Sebesta, C. et al. Subsecond multichannel magnetic control of select neural circuits in freely moving flies. Nat. Mater. 21, 951–958 (2022).
Chen, J. C. et al. A wireless millimetric magnetoelectric implant for the endovascular stimulation of peripheral nerves. Nat. Biomed. Eng. 6, 706–716 (2022).
Jiang, S. et al. Spatially expandable fiber-based probes as a multifunctional deep brain interface. Nat. Commun. 11, 6115 (2020).
Yun, S. H. & Kwok, S. J. J. Light in diagnosis, therapy and surgery. Nat. Biomed. Eng. 1, 0008 (2017).
Jiang, S., Wu, X., Rommelfanger, N. J., Ou, Z. & Hong, G. Shedding light on neurons: optical approaches for neuromodulation. Natl Sci. Rev. 9, nwac007 (2022).
Hong, G., Antaris, A. L. & Dai, H. Near-infrared fluorophores for biomedical imaging. Nat. Biomed. Eng. 1, 0010 (2017).
Zhang, F. et al. Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures. Nat. Protoc. 5, 439–456 (2010).
Keahey, P., Ramalingam, P., Schmeler, K. & Richards-Kortum, R. R. Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents. Proc. Natl Acad. Sci. USA 113, 10769–10773 (2016).
Yang, Y. et al. Preparation and use of wireless reprogrammable multilateral optogenetic devices for behavioral neuroscience. Nat. Protoc. 17, 1073–1096 (2022).
Ausra, J. et al. Wireless, battery-free, subdermally implantable platforms for transcranial and long-range optogenetics in freely moving animals. Proc. Natl Acad. Sci. USA 118, e2025775118 (2021).
Montgomery, K. L. et al. Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice. Nat. Methods 12, 969–974 (2015).
Chen, S. et al. Near-infrared deep brain stimulation via upconversion nanoparticle-mediated optogenetics. Science 359, 679–684 (2018).
Wu, X. et al. Tether-free photothermal deep-brain stimulation in freely behaving mice via wide-field illumination in the near-infrared-II window. Nat. Biomed. Eng. 6, 754–770 (2022).
Ruan, H. et al. Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light. Sci. Adv. 3, eaao5520 (2017).
Hong, G. Seeing the sound. Science 369, 638 (2020).
Wu, X. et al. Sono-optogenetics facilitated by a circulation-delivered rechargeable light source for minimally invasive optogenetics. Proc. Natl Acad. Sci. USA 116, 26332–26342 (2019).
Wang, W. et al. Ultrasound-triggered in situ photon emission for noninvasive optogenetics. J. Am. Chem. Soc. 145, 1097–1107 (2023).
Yang, F. et al. Palette of rechargeable mechanoluminescent fluids produced by a biomineral-inspired suppressed dissolution approach. J. Am. Chem. Soc. 144, 18406–18418 (2022).
Yang, F. et al. A biomineral-inspired approach of synthesizing colloidal persistent phosphors as a multicolor, intravital light source. Sci. Adv. 8, eabo6743 (2022).
Yang, F. et al. Principles and applications of sono-optogenetics. Adv. Drug Deliv. Rev. 194, 114711 (2023).
Zhou, X. X. et al. A single-chain photoswitchable CRISPR-Cas9 architecture for light-inducible gene editing and transcription. ACS Chem. Biol. 13, 443–448 (2018).
Li, X., Lovell, J. F., Yoon, J. & Chen, X. Clinical development and potential of photothermal and photodynamic therapies for cancer. Nat. Rev. Clin. Oncol. 17, 657–674 (2020).
Kim, T.-I. et al. Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science 340, 211–216 (2013).
Salatino, J. W., Ludwig, K. A., Kozai, T. D. Y. & Purcell, E. K. Glial responses to implanted electrodes in the brain. Nat. Biomed. Eng. 1, 862–877 (2017).
Shahriari, D., Rosenfeld, D. & Anikeeva, P. Emerging frontier of peripheral nerve and organ interfaces. Neuron 108, 270–285 (2020).
Hibberd, T. J. et al. Optogenetic induction of colonic motility in mice. Gastroenterology 155, 514–528.e6 (2018).
Xian, Q. et al. Modulation of deep neural circuits with sonogenetics. Proc. Natl Acad. Sci. USA 120, e2220575120 (2023).
Airan, R. D. & Butts Pauly, K. Hearing out ultrasound neuromodulation. Neuron 98, 875–877 (2018).
Sato, T., Shapiro, M. G. & Tsao, D. Y. Ultrasonic neuromodulation causes widespread cortical activation via an indirect auditory mechanism. Neuron 98, 1031–1041.e5 (2018).
Guo, H. et al. Ultrasound produces extensive brain activation via a cochlear pathway. Neuron 98, 1020–1030.e4 (2018).
Mohammadjavadi, M. et al. Elimination of peripheral auditory pathway activation does not affect motor responses from ultrasound neuromodulation. Brain Stimul. 12, 901–910 (2019).
Ye, P. P., Brown, J. R. & Pauly, K. B. Frequency dependence of ultrasound neurostimulation in the mouse brain. Ultrasound Med. Biol. 42, 1512–1530 (2016).
Yang, J.-M. et al. Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo. Nat. Med. 18, 1297–1302 (2012).
Arenkiel, B. R. et al. In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2. Neuron 54, 205–218 (2007).
Kefauver, J. M., Ward, A. B. & Patapoutian, A. Discoveries in structure and physiology of mechanically activated ion channels. Nature 587, 567–576 (2020).
Oh, S.-J. et al. Ultrasonic neuromodulation via astrocytic TRPA1. Curr. Biol. 29, 3386–3401.e8 (2019).
Hu, Z., Chen, S., Yang, Y., Gong, Y. & Chen, H. An affordable and easy-to-use focused ultrasound device for noninvasive and high precision drug delivery to the mouse brain. IEEE Trans. Biomed. Eng. 69, 2723–2732 (2022).

Activation of mechanoluminescent nanotransducers by focused ultrasound enables light delivery to deep-seated tissue in vivo

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