Biodistribution and inflammatory response to intracranial delivery of scintillating nanoparticles

Fischer, Máté; Zimmerman, Amber; Zhang, Eric; Kolis, Joseph W.; Dickey, Ashley; Burdette, Mary K.; Afaghpour-Becklund, Mitra; Chander, Praveen N.; Foulger, Stephen H.; Brigman, Jonathan L.; Weick, Jason P.

doi:10.1101/609354

Cited by 4 publications

(5 citation statements)

References 39 publications

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“…Another advantage of combining x-rays with RLPs is that scintillators can be delivered in extremely close proximity to the cells expressing the opsins and therefore less light is needed to stimulate the opsin. Radioluminescent nanoparticles have been shown to persist in brain tissue for at least 72 h after injection [54], enabling repeated experiments over multiple days. Radioluminescent nanoparticles can also be delivered into the brain using focused ultrasound to open the blood brain barrier [22], avoiding the damage of intracranial injection.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of cerium-doped LSO particles as a scintillator for x-ray induced optogenetics

Bartley¹,

Fischer²,

Bagley³

et al. 2021

J. Neural Eng.

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Optogenetics is a widely used tool for studying neural circuits. However, non-invasive methods for light delivery in the brain are needed to avoid physical damage typically caused by intracranial insertion of light guides. An innovative strategy could employ X-ray activation of radioluminescent particles (RLPs) to emit localized light. We previously reported that RLPs composed of cerium doped lutetium oxyorthosilicate (LSO:Ce), an inorganic scintillator that emits blue light, are biocompatible with neuronal function and synaptic transmission. However, little is known about the consequences of acute X-ray exposure on synaptic function and long-term plasticity. Furthermore, modulation of neuronal or synaptic function by X-ray induced radioluminescence from RLPs has not yet been demonstrated. Here we show that 30 minutes of X-ray exposure at a rate of 0.042 Gy/second caused no change in the strength of basal glutamatergic transmission during extracellular dendritic field recordings in mouse hippocampal slices. Additionally, long-term potentiation (LTP), a robust measure of synaptic integrity, was able to be induced after X-ray exposure and expressed at a magnitude not different from control conditions (absence of X-rays). This is important as synaptic plasticity is critical to learning and memory. Next, we used molecular and electrophysiological approaches to determine if X-ray dependent radioluminescence emitted from RLPs can activate light sensitive proteins. We found that X-ray stimulation of RLPs elevated cAMP levels in HEK293T cells expressing OptoXR, a chimeric opsin receptor that combines the extracellular lightsensitive domain of channelrhodopsin-2 (ChR2) with an intracellular second messenger signaling cascade. This demonstrates that X-ray radioluminescence from LSO:Ce particles can activate OptoXR. Next, we tested whether X-ray activation of the RLPs can enhance synaptic activity in whole-cell recordings from hippocampal neurons expressing ChR2, both in cell culture and acute hippocampal slices. Importantly, Xray radioluminescence caused an increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in both systems, indicating activation of ChR2 and excitation of neurons. Together, our results show that X-ray activation of LSO:Ce particles can heighten cellular and synaptic function. The combination of LSO:Ce inorganic scintillators and X-rays is therefore a viable method for optogenetics as an alternative to more invasive light delivery methods.

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Section: Discussionmentioning

confidence: 99%

Feasibility of cerium-doped LSO particles as a scintillator for x-ray induced optogenetics

Bartley¹,

Fischer²,

Bagley³

et al. 2021

J. Neural Eng.

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“…The injectability of Au@DH−CNO and Au@LC−CNO was studied in PBS (10 mM, pH 7.2) using a stereotaxic injection syringe at a flow rate of 10 μL/ min (Toelting quintessential stereotaxic injector). 23 In Vitro Aggregation of Hen Egg White Lysozyme (HEWL A ) and Amyloid β 42 (Aβ42 A ). In the literature, hen egg white lysozyme (HEWL) fibrillation was achieved at different time intervals, viz., ∼1 h, 5 h, and even after 12 days of incubation.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…The injectability of Au@DH–CNO and Au@LC–CNO was studied in PBS (10 mM, pH 7.2) using a stereotaxic injection syringe at a flow rate of 10 μL/min (Toelting quintessential stereotaxic injector) …”

Section: Methodsmentioning

confidence: 99%

Multifunctional Gold Nanoparticle-Conjugated Cellulose Nanoonions Alleviate Aβ42 Fibrillation-Induced Toxicity via Regulation of Oxidative Stress and Ion Homeostasis

2021

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Inhibition of hen egg white lysozyme (HEWL) and Aβ42 fibrillation have been established as the main models for the treatment of systemic lysozyme amyloidosis and Alzheimer’s disease (AD), respectively. Several antiamyloidogenic nanomaterials have been developed over the period; however, their intracellular mechanism of action is still not well understood. In this context, plant-based, gold-conjugated, injectable, hydrophilic cellulose nanoonions (CNOs), viz., DH–CNO (∼60 ± 5 nm) and LC–CNO (∼55 ± 12 nm), were developed from their respective hydrophobic cellulose nanocrystals (DH–CNC and LC–CNC) using a single-step chemical template-mediated process. This unique nanocellulose architecture was chemically and morphologically characterized by various spectroscopic and microscopic techniques. Further, the different biophysical studies documented marked the inhibition/disintegration potential of gold-conjugated LC–CNO against HEWL and Aβ42 peptide aggregation. It was further observed that inhibition of protein fibrillation could be achieved within ∼10 min when the same materials were used under photoirradiation conditions. In vitro protein aggregation studies using HEK293 cells suggested that gold-conjugated LC–CNO could effectively reduce the cellular toxicity via regulation of oxidative stress and ion homeostasis. The outcome of the present study will help in designing cellulose-based novel functional nanochaperones against various neurodegenerative diseases.

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“…To enhance curcumin solubility, Rahman et al [ 118 ] produced β-cyclodextrincurcumin binding interactions that incorporated both natural curcumin and the complexes independently into liposomes. Entire curcumin-containing preparations were efficient at suppressing cell growth in vitro cell study [ 119 ]. Shi et al [ 120 ] used an enzyme-linked immunosorbent assay (ELISA) technique to evaluate curcumin’s therapeutic benefits on lung fibrosis in mice using a water-soluble liposomal curcumin that was found to successfully reduce radiation pneumonitis and lung fibrosis and sensitize LL/2 cells to irradiation.…”

Section: Various Nano Drug Delivery Systems For Curcuminmentioning

confidence: 99%

The Multifaceted Role of Curcumin in Advanced Nanocurcumin Form in the Treatment and Management of Chronic Disorders

Tagde

Tagde²,

Islam

et al. 2021

Molecules

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Curcumin is the primary polyphenol in turmeric’s curcuminoid class. It has a wide range of therapeutic applications, such as anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers, but has poor solubility and low bioavailability. Objective: To improve curcumin’s bioavailability, plasma concentration, and cellular permeability processes. The nanocurcumin approach over curcumin has been proven appropriate for encapsulating or loading curcumin (nanocurcumin) to increase its therapeutic potential. Conclusion: Though incorporating curcumin into nanocurcumin form may be a viable method for overcoming its intrinsic limitations, and there are reasonable concerns regarding its toxicological safety once it enters biological pathways. This review article mainly highlights the therapeutic benefits of nanocurcumin over curcumin.

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Biodistribution and inflammatory response to intracranial delivery of scintillating nanoparticles

Cited by 4 publications

References 39 publications

Feasibility of cerium-doped LSO particles as a scintillator for x-ray induced optogenetics

Feasibility of cerium-doped LSO particles as a scintillator for x-ray induced optogenetics

Multifunctional Gold Nanoparticle-Conjugated Cellulose Nanoonions Alleviate Aβ42 Fibrillation-Induced Toxicity via Regulation of Oxidative Stress and Ion Homeostasis

The Multifaceted Role of Curcumin in Advanced Nanocurcumin Form in the Treatment and Management of Chronic Disorders

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