Expanding the Toolbox of Upconversion Nanoparticles for In Vivo Optogenetics and Neuromodulation

Abstract

Optogenetics is an optical technique that exploits visible light for selective neuromodulation with spatio-temporal precision. Despite enormous effort, the effective stimulation of targeted neurons, which are located in deeper structures of the nervous system, by visible light, remains a technical challenge. Compared to visible light, near-infrared illumination offers a higher depth of tissue penetration owing to a lower degree of light attenuation. Herein, an overview of advances in developing new modalities for neural circuitry modulation utilizing upconversion-nanoparticlemediated optogenetics is presented. These developments have led to minimally invasive optical stimulation and inhibition of neurons with substantially improved selectivity, sensitivity, and spatial resolution. The focus is to provide a comprehensive review of the mechanistic basis for evaluating upconversion parameters, which will be useful in designing, executing, and reporting optogenetic experiments.

Recent advance of carbon dots in bio-related applications

“…To enhance the cellular uptake or the EPR, Hou et al [183] conjugated the carboxylate CDs with PLGA-b-PEG-NH 2 through growth curves (n = 5) observed after different treatments (n = 5, P < 0.05 for each group); (g) the relative body weights of the nude mice increased continuously after different treatments; (h) representative photographs of the four groups after different treatments; (i) H&E stained images of tumors of the four groups after different treatments [150]. Reproduced from [11] with permission of The Royal Society of Chemistry. the bioconjugation.…”

“…Among these imaging modalities, fluorescent imaging technique carry significant weight, because of their high sensitivity, high resolution, affordable instruments and easy observation. A diverse set of fluorescent probes have been explored for fluorescent bioimaging, such as organic fluorescent molecules [1], quantum dots [2,3], gold nanocluster [4,5], aggregation-induced emission (AIE) nanoparticles [6,7], near-infrared dyes or nanoparticles [8], and up-conversion nanoparticles [9][10][11]. Beyond bioimaging, these fluorescent probes can be combined with other functionalities to create dual/multi-imaging probes, targeted imaging units, or theragnostic agents to performance multiple functions at once [12].…”

Advanced Near‐Infrared Light for Monitoring and Modulating the Spatiotemporal Dynamics of Cell Functions in Living Systems

“…First, upconversion nanoparticles (UCNPs) can be excited by NIR light, for example, 980 nm or longer wavelength, and emit ultraviolet (UV) or visible light that can active light‐sensitive protein‐ion channels in genetically engineered cells, offering a possibility of operating optogenetic researches with high tissue penetration depth NIR‐II light. [ 48,28 ] Second, a series of photothermal nanomaterials, including Au nanomaterials and organic semiconducting nanomaterials, are capable of generating local heat in cells during NIR light irradiation. [ 49,50 ] Thereby, a series of temperature‐dependent biological processes can be modulated by the generated heat, such as photothermal cell killing, heat‐related gene expression, heat‐controlled drug release, and photothermal neuron activation.…”

“…Currently, NIR‐light‐mediated regulations of gene expression were mainly achieved through NIR light nanotransducers, such as upconversion nanoparticles (UCNPs), gold nanorods (AuNRs), and photothermal polymers. [ 5,42,48,49 ]…”

“…Subsequently, the UV or visible light can be utilized to control the optogenetic channel proteins and photosensitive polymers, thus regulating the gene expression of target cells. [ 48 ] In recent years, UCNP‐mediated optogenetics has been widely reported. For example, Chen and colleagues reported a UCNP‐based siRNA nanocarrier system for spatiotemporally control of gene silencing in MDA‐MB‐468 TNBC cells.…”