Researchers use biocompatible polydopamine nanoparticles and near-infrared light to remotely trigger activity in neuron and muscle cells with minimal side effects.
(Nanowerk Spotlight) Remote control over the behavior of individual cells has remained one of the more difficult problems in neuroscience and muscle physiology. The ability to activate, suppress, or modulate the function of single cells would offer powerful new tools for understanding how tissues operate, how diseases progress, and how targeted interventions might be designed.
In neurological disorders, for instance, it could allow selective reactivation of silent neural circuits without affecting neighboring cells. In muscle repair, it could help retrain or regenerate specific fibers. Such precise control would also aid in mapping brain function, studying cell signaling, and engineering artificial tissues with programmable behavior.
Despite its appeal, this level of control has proven hard to achieve. Conventional methods struggle to combine the safety of noninvasive techniques with the specificity required for targeting single cells. Invasive procedures like deep brain stimulation deliver localized effects but require surgery and carry risks of inflammation and tissue damage. Noninvasive methods, such as transcranial magnetic stimulation or direct current stimulation, reduce these risks but lack the spatial resolution to reliably affect only the intended cells.
Efforts to improve this tradeoff have led to interest in light-based methods. Optogenetics, which uses genetic modification to introduce light-sensitive proteins into cells, can achieve high precision using targeted light pulses. But optogenetics still requires gene delivery through viral vectors or transgenic models, making it less practical for therapeutic use. It also depends on visible light, which doesn’t penetrate deeply into tissue, limiting its usefulness in vivo.
Nanoparticles that respond to external stimuli have been explored as a possible bridge between noninvasive and precise control. Among these are magnetic nanoparticles that heat up in response to magnetic fields, or piezoelectric particles that generate electric charges when mechanically stressed. But these systems are often limited by the strength of the field or force needed, and concerns remain about the safety of using inorganic materials that do not break down easily in the body.
One promising direction involves using nanoparticles that convert near-infrared (NIR) light into heat. NIR light penetrates deeper into tissue than visible light and can be applied with spatial and temporal control. Gold nanoparticles have been used for this purpose, but their low biodegradability and potential to trigger oxidative stress after heating are obstacles to long-term or repeated use.
In a recent study published in ACS Nano (“Cellular Activity Modulation Mediated by Near Infrared-Irradiated Polydopamine Nanoparticles: In Vitro and Ex Vivo Investigation”), researchers from the Istituto Italiano di Tecnologia and colleagues in Japan reported a new system based on fully organic polydopamine nanoparticles (PDNPs). These are made from a synthetic form of dopamine, a natural molecule found in the brain, and have favorable properties including biocompatibility, antioxidant activity, and efficient conversion of NIR light into heat. The team tested whether these particles could activate individual neuron-like and muscle cells in a controlled and repeatable way, without damaging the cells or introducing harmful side effects.
Schematic representation of polydopamine nanoparticle-mediated photothermal stimulation. Upon near-infrared (NIR) laser exposure, polydopamine nanoparticles (PDNPs) internalized by neuron-like cells, skeletal muscle cells, or Drosophila brain tissue generate localized heating that modulates cellular activity. In neurons, stimulation triggers acetylcholine release and increases in intracellular calcium levels. In muscle cells, it induces targeted contractions. This approach enables precise, noninvasive control of cell behavior using a fully organic photothermal system. (Image: Reprinted from DOI:10.1021/acsnano.5c04181, CC-BY 4.0)
The researchers worked with two standard cell types: SH-SY5Y cells, which serve as a model for neurons, and C2C12 cells, which can develop into muscle fibers. The PDNPs were small, uniform, and stable in biological fluids. They were readily taken up by both types of cells, collecting mostly in lysosomes. Muscle cells took up more particles than neuron-like cells, which meant they responded to lower laser power during experiments.
To test the effect of light exposure, the team used a laser emitting NIR light focused on a tiny area of the cell. In the absence of PDNPs, this light produced no temperature change. But when cells had internalized the particles, short laser pulses produced rapid and localized heating, raising the temperature by about 4-6°C, enough to activate heat-sensitive ion channels in the cell membrane.
In neuron-like cells, this thermal effect triggered a sharp increase in calcium levels—a common signal for cell activation. The researchers confirmed this by measuring changes in fluorescence using a calcium-sensitive dye. When they blocked calcium channels or removed external calcium, the effect was significantly reduced or eliminated, showing that the rise in calcium came largely from outside the cell and required functioning ion channels.
They also applied a pattern of repeated brief laser pulses, which led to a much stronger calcium response, not just in the targeted cells but occasionally in nearby ones as well. This suggested the stimulated cells were releasing acetylcholine, a neurotransmitter that can activate neighboring neurons. To verify this, they used a biosensor that lights up in the presence of acetylcholine. Fluorescence increased only in PDNP-treated cells during laser stimulation, confirming release of the neurotransmitter.
Similar results were observed in muscle cells. The local heating caused contractions confined to the irradiated region, consistent with a temperature-sensitive mechanism rather than a global electrical signal. The effect depended on myosin, the protein responsible for muscle contraction, and was abolished when myosin activity was blocked. The researchers found that the extent of contraction closely tracked the increase in temperature.
A major concern with any heating-based method is the risk of oxidative stress—cellular damage caused by reactive oxygen species (ROS) that are often produced when cells are exposed to high temperatures. The team compared PDNPs with gold nanoparticles known to induce oxidative stress under similar conditions. In both neuron-like and muscle cells, gold particles caused a sharp rise in ROS levels following NIR exposure. PDNPs, on the other hand, did not. In neurons, there was a small, short-lived increase in ROS that quickly returned to baseline. In muscle cells, no significant change in ROS was detected. This is likely due to the antioxidant properties of polydopamine, which neutralize free radicals before they can damage the cell.
To assess whether these effects influenced longer-term cell behavior, the researchers performed a proteomic analysis to measure changes in protein expression. In neuron-like cells, treatment with PDNPs—especially when combined with NIR stimulation—boosted proteins linked to brain development, synapse formation, and calcium signaling. Some of the most affected proteins are known to support neural repair and plasticity. In muscle cells, PDNP treatment increased proteins involved in muscle structure, metabolic balance, and differentiation, including those critical for energy use and growth.
These protein changes suggest that PDNPs not only trigger short-term responses but may also shape the way cells grow and function over time. In neurons, they enhanced outgrowth and branching of nerve fibers, key markers of maturation and network formation. In muscle cells, although the visible morphology didn’t change dramatically, there was a shift in protein profiles associated with muscle stability and responsiveness.
The study also extended the results to brain tissue from Drosophila melanogaster, a model organism commonly used in neuroscience. In fly brains expressing a calcium-sensitive fluorescent protein, PDNP-mediated NIR stimulation caused clear increases in calcium signaling. When acetylcholine breakdown was inhibited, this response was prolonged, indicating sustained neurotransmitter release. When acetylcholine receptors were blocked, the signal was reduced, confirming the importance of synaptic transmission in the observed effects.
By combining organic nanoparticles with targeted light exposure, the researchers demonstrated a precise, noninvasive method for controlling the behavior of individual cells. Unlike earlier systems that required genetic engineering, surgical implants, or inorganic materials, this approach relies on biodegradable components and light that can pass through tissue. It allows not just activation of neurons and muscle cells but also supports changes in gene expression that could aid in tissue regeneration or repair.
This study introduces a platform that could serve both as a tool for research and as a foundation for developing therapies that require fine-grained control over biological systems. It may eventually help in creating more precise neural interfaces, guiding the growth of engineered tissues, or improving the study of neural circuits without genetic modification.
“Our work shows that it is possible to control the activity of individual neurons and muscle cells with high precision—without invasive intervention or genetic modification—using fully organic, biodegradable nanoparticles and harmless light,” Dr. Gianni Ciofani, who led this work, concludes. “This opens a new path toward safer, more targeted therapies for neurological and muscular disorders.”
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