Electro-optical Neural Platform Integrated with Nanoplasmonic Inhibition Interface

Engineering of neural interfaces with nanomaterials for remote manipulation facilitates the development of platforms for the study and treatment of brain disorders, yet extending their capability to inhibiting the electrical activities of unmodified neurons has been difficult. Here we report the development of an electro-optical neural platform integrated with gold nanorods for simultaneous electrical excitation and readout, and photothermal inhibition of neural activities. A monolayer of gold nanorods was placed at the electrode–neuron interfaces of a microelectrode array for photothermal stimulation of neural activities. This nanoplasmonic interface interacted well with neurons and metal electrodes without affecting the biological and electrical properties. We demonstrated that spontaneous firing of neurons and their signal propagation along the neurites evoked by electrical stimulation were optically inhibited on this neural platform. We believe that our platform could be an alternative to the optogenetic approach and may ultimately be applied to prosthetic devices based on optical neuromodulation

Nanoplasmonic Detection of EGFR Mutations Based on Extracellular Vesicle-Derived EGFR–Drug Interaction

Analysis of membrane proteins from extracellular vesicles (EVs) has emerged as an important strategy for molecular cancer diagnosis. The epidermal growth factor receptor (EGFR) is one of the most well-known oncogenic membrane proteins, particularly in non-small cell lung cancer (NSCLC), where targeted therapies using tyrosine kinase inhibitors (TKIs) are often addressed based on EGFR mutation status. Consequently, several studies aimed at analyzing oncogenic membrane proteins have been proposed for cancer diagnosis. However, conventional protein analysis still faces limitations due to the requirement for large sample quantities and extensive post-labeling processes. Here, we develop a nanoplasmonic detection method for EGFR mutations in the diagnosis of NSCLC based on interactions between EGFR loaded in EVs and TKI. Gefitinib is selected as a model TKI due to its strong signals in the surface-enhanced Raman spectroscopy (SERS) and mutation-dependent binding affinity to EGFR. We demonstrate an SERS signal attributed to gefitinib at a higher value in the EGFR exon 19 deletion, both in cells and EVs, compared to wild-type and exon 19 deletion/T790M variants. Furthermore, we observe a significantly higher gefitinib SERS signal in EGFR obtained from exon 19 deletion NSCLC patient plasma-derived EVs compared with those from wild-type and exon 19 deletion/T790M EVs. Since our approach utilizes an analysis of the SERS signal generated by the interaction between oncogenic membrane proteins within EVs and targeted drugs, its diagnostic applicability could potentially extend to other liquid biopsy methods based on EVs

Liposomal Indocyanine Green for Enhanced Photothermal Therapy

In this study, we engineered liposomal indocyanine green (ICG) to maximize its photothermal effects while maintaining the fluorescence intensity. Various liposomal formulations of ICG were prepared by varying the lipid composition and the molar ratio between total lipid and ICG, and their photothermal characteristics were evaluated under near-infrared irradiation. We showed that the ICG dispersity in the liposomal membrane and its physical interaction with phospholipids were the main factors determining the photothermal conversion efficiency. In phototherapeutic studies, the optimized formulation of liposomal ICG showed greater anticancer effects in a mouse tumor model compared with other liposomal formulations and the free form of ICG. Furthermore, we utilized liposomal ICG to visualize the metastatic lymph node around the primary tumor under fluorescence imaging guidance and ablate the lymph node with the enhanced photothermal effect, indicating the potential for selective treatment of metastatic lymph node

Photothermal Inhibition of Neural Activity with Near-Infrared-Sensitive Nanotransducers

A neural stimulation technique that can inhibit neural activity reversibly and directly without genetic modification is valuable for understating complex brain functions and treating brain diseases. Here, we propose a near-infrared (NIR)-activatable nanoplasmonic technique that can inhibit the electrical activity of neurons by utilizing gold nanorods (GNRs) as photothermal transducers on cellular membranes. The GNRs were bound onto the plasma membrane of neurons and irradiated with NIR light to induce GNR-mediated photothermal heating near the membrane. The electrical activity from the cultured neuronal networks pretreated with GNRs was immediately inhibited upon NIR irradiation, and fully restored when NIR light was removed. The degree of inhibition could be precisely modulated by tuning the laser intensity, thereby enabling restoration of firing of a hyperactive neuronal network with epileptiform activity. This nanotechnological approach to inhibit neural activity provides a powerful therapeutic platform to control cellular functions associated with disordered neural circuits

<i>In Vivo</i> Clearance and Toxicity of Monodisperse Iron Oxide Nanocrystals

Thermal decomposition of organometallic precursors has been found to generate highly crystalline iron oxide (IO) nanocrystals that display superior MR contrast and lower polydispersity than IO nanocrystals synthesized by aqueous precipitation. In the present study, the <i>in vivo</i> characteristics of IO nanocrystals prepared by the thermal decomposition route and then coated with a phospholipid containing a pendant poly(ethylene glycol) chain are examined. The size and surface chemistry of the IO nanocrystal influence the biodistibution, the rate of biodegradation and bioclearance, and the biodegradation products. We conclude that the <i>in vivo</i> fate of PEGylated monodisperse IO nanocrystals and the iron, phospholipid, and oleic acid biodegradation products may influence the cellular environments in the organs and blood that can determine their safety in the body

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In vivo real-time visualization of intravenously injected free-form ICG in liver (Magnified View

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In vivo real-time visualization of intravenously injected free-from ICG in live

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In vivo real-time visualization of intravenously injected liposomal ICG in live

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In vivo real-time visualization of intravenously injected free-form ICG in blood circulation in ski

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In vivo real-time visualization of intravenously injected liposomal ICG in liver (Magnified View