Mechanoluminescent nanoparticles as an energy relay for minimally invasive light delivery in vivo

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Abstract/Contents

Abstract
Optogenetics has revolutionized neuroscience research and has quickly become a ubiquitous tool for the interrogation of neural circuits and the elucidation of the neural underpinnings of behavior. With optogenetics, researchers are able to activate or silence targeted neurons in a rapid and repeatable manner using light as the input signal to control cells expressing light-gated ion channels termed "opsins". The use of light as the input affords excellent temporal control for driving neural activity with millisecond-timescale precision. However, opsins must be activated by light in the visible spectrum, which suffers from extremely poor penetration depths in biological tissues. Therefore, visible light is ordinarily delivered through macroscopic light sources such as optical fibers or LEDs implanted directly into the brain. Along with the acute trauma associated with the highly invasive implantation procedure, the presence of these large foreign bodies in neural tissue elicits chronic immune responses and perturbs endogenous neural physiology. Herein, I detail a novel strategy for in vivo light delivery through the use of intravenously administered mechanoluminescent nanoparticles coupled with focused ultrasound which exhibits exceptional transmission through biological tissues. Mechanoluminescent nanoparticles in the blood circulation are charged with photoexcitation light while passing through superficial blood vessels and store the energy from the absorbed light until application of focused ultrasound, which then triggers the release of the stored energy in the form of visible light emission. This process of charging and discharging can be repeated indefinitely while the nanoparticles circulate through the body, allowing for controllable, repetitive visible light emission in the brain. In this way, mechanoluminescent nanoparticles act as an energy relay for light delivery through the blood circulatory system. Due to the densely distributed cerebral vasculature and microvasculature, the nanoparticles are able to illuminate any region of the brain controlled by the location of ultrasound focus, while the application of ultrasound is accomplished through the intact scalp and skull to minimize any damage to the brain tissue. Therefore, compared to the conventional method of light delivery for optogenetics, this strategy allows for a much less invasive interface for risk-averse optogenetic neuromodulation.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2023; ©2023
Publication date 2023; 2023
Issuance monographic
Language English

Creators/Contributors

Author Chong, Paul, (Researcher in chemistry)
Degree supervisor Hong, Guosong
Thesis advisor Hong, Guosong
Thesis advisor Cui, Bianxiao
Thesis advisor Zare, Richard N
Degree committee member Cui, Bianxiao
Degree committee member Zare, Richard N
Associated with Stanford University, School of Humanities and Sciences
Associated with Stanford University, Department of Chemistry

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Paul Chong.
Note Submitted to the Department of Chemistry.
Thesis Thesis Ph.D. Stanford University 2023.
Location https://purl.stanford.edu/py246tt3014

Access conditions

Copyright
© 2023 by Paul Chong
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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