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Characterization of the anti-ICG-micelles. (a) Particle size distributions of the ICG-micelles (black line) and anti-ICG-micelles (red line) in ultrapure water, as measured by DLS. (b) NIR-induced photothermal effect against ND7/23 cells. Cytotoxicity was evaluated by performing WST assays. The data are presented as the mean ± SD (n = 4).
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In this study, we developed a novel biodegradable/photothermal polymer micelle-based remote-activation method for a temperature-sensitive ion channel, namely transient receptor potential cation channel subfamily V member 1 (TRPV1). Biodegradable/photothermal polymer micelles containing indocyanine green (ICG-micelles) were prepared using a simple o...
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... study the NIR light-induced activation of the TRPV1 channel on neuronal cells, anti-TRPV1 antibody-labelled ICGmicelles (anti-ICG-micelles) were prepared via almost the same method used to prepare anti-NR-micelles, as described above. The particle size of the anti-ICG-micelles was characterised by DLS ( Fig. 5(a)). Our results showed that, after antibody conjugation, the hydrodynamic diameter of the micelles increased slightly from approximately 35 nm (ICG-micelles) to approximately 40 nm (anti-ICG-micelles). This difference likely reflects antibody conjugation on the micelle surface. Furthermore, antibody conjugation on the micelle surface was ...
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... the phototoxicity of the anti-ICG-micelles against neurons after NIR irradiation was evaluated by performing WST assays (Fig. 5(b)). The NIR light-induced photothermal effect is used for cancer therapy where an elevated temperature causes cancer cell death. 35 Therefore, appropriate laser strength and irradiation time are required for safe activation of the TRPV1 channel. Fig. 5(b) shows the WST assay results obtained after treating ND7/23 cells with ...
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... against neurons after NIR irradiation was evaluated by performing WST assays (Fig. 5(b)). The NIR light-induced photothermal effect is used for cancer therapy where an elevated temperature causes cancer cell death. 35 Therefore, appropriate laser strength and irradiation time are required for safe activation of the TRPV1 channel. Fig. 5(b) shows the WST assay results obtained after treating ND7/23 cells with anti-ICGmicelles and subsequent NIR irradiation. The micelle concentration, laser strength, and irradiation time were 50 μg mL −1 (on ICG), 1 W cm −2 , and 3 min, respectively. Treatment with NIR laser irradiation alone showed almost no phototoxicity. In addition, ...
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... did not show obvious cytotoxicity after NIR laser irradiation. As shown in Fig. 2(g), the ICG-micelle samples showed an NIR light induced photothermal temperature increase in the cuvette with magnetic stirring at same micelle concentration, laser strength, and irradiation time of cell experiment. However, in the case of cell experiment (Fig. 5(b)), before NIR irradiation, the ICG-micelle added cells were washed with PBS and the unconjugated ICG-micelles were removed from the cells. Thus, the ICG concentration of the cell experiment samples were probably reduced as compared to the temperature measurement samples in the cuvette. In addition, because of the adhered cell samples ...
Citations
... NIR/Red light activate TRPV1 TRPV1, a nonselective cation channel (Zupin et al., 2021). NIR (740-1100 nm) induces TRPV1 opening and calcium influx (Chen et al., 2022a), thereby serving as a potential therapeutic approach for brain disorders via TRPV1 (Kwon et al., 2021) ...
... The release of NR from the PSt NP was examined in ultrapure water at 14-37°C using dialysis using a membrane (MWCO : 3,500). [27] At defined time intervals (0-24 h), 1 mL of dialysate solution was obtained and replaced with an equal volume of fresh media. NR concentration in the dialysate samples was determined spectrophotometrically by measuring the absorbance at 540 nm. ...
Liquid‐liquid phase separation (LLPS) in living cells has received considerable attention in the biomedical research field. This study is the first to report nanoparticle (NP) uptake into LLPS droplets. Fluorescent dye, Nile red loaded polystyrene NPs (NR‐PSt NPs) uptake into model LLPS droplets consisting of adenosine triphosphate (ATP) and poly‐L‐lysine (PLL) was visualized using fluorescence imaging. Fluorescence imaging showed that the LLPS droplets had a quick NP uptake behavior. Furthermore, temperature changes (4–37 °C) significantly affected the NP uptake behavior of the LLPS droplets. Moreover, the NP‐incorporated droplets displayed high stability under strong ionic strength conditions (1 M NaCl). ATP measurements displayed that ATP was released from the NP‐incorporated droplets, indicating that the weakly negatively charged ATP molecules and strongly negatively charged NPs were exchanged, which resulted in the high stability of the LLPS droplets. These fundamental findings will contribute to the LLPS studies using various NPs.
... TRPV1) which can then be targeted by polymeric nanoparticles exhibiting excellent photothermal properties, enabling heat generation with NIR activation at low power densities and thereby preserving tissue health. 82,83 However, such depolarisation is only transient as longer irradiation exposures can instead induce membrane hyperpolarisation and suppress synaptic activity. 84 Nevertheless, transcranial NIR stimulation has been investigated in several clinical trials to treat neurological disorders including depression, anxiety, and AD. ...
Neurological disorders are one of the world's leading medical and societal challenges due to the lack of efficacy of the first line treatment. Although pharmacological and non-pharmacological interventions have been employed with the aim of regulating neuronal activity and survival, they have failed to avoid symptom relapse and disease progression in the vast majority of patients. In the last 5 years, advanced drug delivery systems delivering bioactive molecules and neuromodulation strategies have been developed to promote tissue regeneration and remodel neuronal circuitry. However, both approaches still have limited spatial and temporal precision over the desired target regions. While external stimuli such as electromagnetic fields and ultrasound have been employed in the clinic for non-invasive neuromodulation, they do not have the capability of offering single-cell spatial resolution as light stimulation. Herein, we review the latest progress in this area of study and discuss the prospects of using light-responsive nanomaterials to achieve on-demand delivery of drugs and neuromodulation, with the aim of achieving brain stimulation and regeneration.
In this study, we have developed the activation method of thermo-responsive TRPV1 ion channels of neurons using photothermal and biodegradable polymer micelles. Indocyanine Green (ICG) dye was loaded on polymer micelles formed from poly(ethylene glycol) block copolymer possessing poly(lactic-co-glycolic acid) (PEG-b-PLGA) segment. The obtained ICG-loaded micelles showed a photothermal effect under tissue penetrable near-infrared (NIR) light irradiation. In addition, the ICG micelles also displayed biodegradability in acidic conditions. Furthermore, anti-TRPV1 antibody installed ICG-micelles showed specific recognition against TRPV1 on the cell membrane and accelerated Na⁺ influx into the cells was observed under NIR irradiation. Based on these results, the ICG micelles developed in this study are expected to be used as a tool for the remote activation of neurons, and they can be applied for various manipulation and analytical techniques of the nervous system.
Ion channel are responsible for the propagation and integration of electrical signals in physiological processes. Over‐activation or dysfunction of ion channel plays an important role in physiological and pathological processes and is an important research object for disease treatment. With the widespread application of optical technologies of near infrared (NIR) light responsive materials, the precise regulation of biological processes through optical control, featuring non‐invasive, remote control, and high flexibility, has penetrated the physiological processes. In recent years, an increasing number of light‐stimulated materials have been developed and utilized, with stable properties, easy modification, and sensitive response, enabling precise control of biological processes at the forefront of biomedical research. This review summarizes NIR responsive materials in ion channel regulation and elucidates their action mechanism in regulating ion channel‐related diseases. It is hoped that this review can provide foundation of research for future light‐stimulated materials, promote the application of light‐stimulated materials in biomedical engineering, and be useful for clinical disease treatment.
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Here, the study presents a thermally activated cell‐signal imaging (TACSI) microrobot, capable of photothermal actuation, sensing, and light‐driven locomotion. The plasmonic soft microrobot is specifically designed for thermal stimulation of mammalian cells to investigate cell behavior under heat active conditions. Due to the integrated thermosensitive fluorescence probe, Rhodamine B, the system allows dynamic measurement of induced temperature changes. TACSI microrobots show excellent biocompatibility over 72 h in vitro, and they are capable of thermally activating single cells to cell clusters. Locomotion in a 3D workspace is achieved by relying on thermophoretic convection, and the microrobot speed is controlled within a range of 5–65 µm s⁻¹. In addition, light‐driven actuation enables spatiotemporal control of the microrobot temperature up to a maximum of 60 °C. Using TACSI microrobots, this study targets single cells within a large population, and demonstrates thermal cell stimulation using calcium signaling as a biological output. Initial studies with human embryonic kidney 293 cells indicate a dose dependent change in intracellular calcium content within the photothermally controlled temperature range of 37–57 °C.
For a long time, optical imaging of the deep brain with high resolution has been a challenge. Recently, with the advance in second near‐infrared (NIR‐II) bioimaging techniques and imaging contrast agents, NIR‐II window bioimaging has attracted great attention to monitoring deeper biological or pathophysiological processes with high signal‐to‐noise ratio (SNR) and spatiotemporal resolution. Assisted with NIR‐II bioimaging, the modulation of structure and function of brain is promising to be noninvasive and more precise. Herein, in this review, first the advantage of NIR‐II light in brain imaging from the interaction between NIR‐II and tissue is elaborated. Then, several specific NIR‐II bioimaging technologies are introduced, including NIR‐II fluorescence imaging, multiphoton fluorescence imaging, and photoacoustic imaging. Furthermore, the corresponding contrast agents are summarized. Next, the application of various NIR‐II bioimaging technologies in visualizing the characteristics of cerebrovascular network and monitoring the changes of the pathology signals will be presented. After that, the modulation of brain structure and function based on NIR‐II bioimaging will be discussed, including treatment of glioblastoma, guidance of cell transplantation, and neuromodulation. In the end, future perspectives that would help improve the clinical translation of NIR‐II light are proposed.
Photobiomodulation (otherwise known as low level light therapy) is an emerging approach for treating many diseases and conditions such as pain, inflammation, wound healing, brain disorders, hair regrowth etc. The light used in this therapy generally lies in the red and near-infrared spectral regions. Despite many positive studies for treating different conditions, this therapy still faces some skepticism, which has prevented its widespread adoption in clinics. The main reasons behind this skepticism are the lack of comprehensive information about the molecular, cellular, and tissular mechanisms of action, which underpin the positive effects of photobiomodulation. Moreover, there is also another therapeutic application using longer wavelength infrared radiation, involving either infrared saunas or heat lamps which are powered by electricity, as well as infrared emitting textiles and garments which are solely powered by the wearer's own body heat. In recent years, much knowledge has been gained about the mechanism of action underlying these treatments, which will be summarized in this review. There are three broad classes of primary chromophores, which have so far been identified. One is mitochondrial cytochromes (including cytochrome c oxidase), another is opsins and light or heat-sensitive calcium ion channels, and a third is nanostructured water clusters. Light sensitive ion channels are activated by the absorption of light by the chromophore proteins, opsin-3 and opsin-4, while mitochondrial chromophores are activated by red or near-infra red (NIR) light up to about 850 nm. However NIR light at 980 nm or longer wavelengths can activate transient receptor potential (TRP) ion channels, probably after being absorbed by nanostructured water clusters. Heat-activated TRP channels undergo a conformational change triggered by only small temperature changes. Here we will discuss the role of opsins and light or heat activated TRP channels in the mechanism of photobiomodulation and infrared therapy.
