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This article, reported by Peng Fei from Sun Yat-sen University, Tu Yingfeng from Southern Medical University, and Zhou Yicheng from Sun Yat-sen University, from the perspective of nanomotor biomaterials, the most significant highlight of this work is not the traditional "delivery of antidepressant drugs", but rather it proposes a new concept that is more focused on physical and chemical regulation: using the near-infrared responsive photochemical nanomotor IC@His-ICG to regulate the molecular polarity dynamics in the neural microenvironment, thereby influencing the excitability of neurons and depressive/anxiety-like behaviors.
In terms of material design, the authors used the tannic acid/zinc coordination complex EA/Zn as the core IC that can induce polarity changes, and then self-assembled poly-L-histidine (His) and indocyanine green ICG to form the IC@His-ICG nanomotor. Among them, ICG shifts the response wavelength to the near-infrared region, and His increases the colloidal stability of the system; under 808 nm near-infrared light irradiation, IC undergoes photochemical reactions, including ester bond hydrolysis and single bond rotation, causing a significant change in the molecular dipole moment, thereby generating "polarity-driven" phototactic movement. More importantly, this movement mechanism does not rely on traditional chemical fuels and can still maintain directional movement in plasma/protein-rich environments such as PBS, DMEM, FBS, and even diluted blood, which is crucial for neural interface materials.
In terms of mechanism, the thinking of this article is very new: the authors do not activate neurons through ligand-receptor, drug-target, or traditional electrode stimulation, but directly regulate the excitability of neurons by the light-induced polarity switching of the nanomotor. In vitro experiments show that after IC@His-ICG is co-localized with the neuronal membrane, it can induce calcium ion influx and temporally and spatially controllable calcium wave oscillations, and upregulate the neuronal activation marker c-Fos; the ROS clearance control proves that this process mainly originates from polarity changes, rather than light by-products or oxidative stress. In other words, this article truly intends to present a "polarity neural regulation" paradigm: using molecular polarity changes at the nanoscale to撬动cell-scale calcium signals and neural excitation conduction.
The animal experiment part further puts the material mechanism into behavioral results. The authors used IC@His-ICG in the corticosterone-induced depression model mice， and through spatially targeted near-infrared light regulation， open field， elevated cross maze， tail suspension， and forced swimming experiments all showed improved anxiety/depression-like behaviors. At the same time， the levels of 5-HT and DA in the brain returned to normal， and the abnormally elevated CRH was downregulated， indicating that this nanomotor regulation is not just a transient stimulation， but can further affect the homeostasis of monoamine neurotransmitters and the output of emotional behaviors. Overall， this is a very imaginative study on photochemical nanomotor + polarity regulation + neural excitation + antidepressant behavior， advancing nanomotors from "delivery tools" to "programmable neural regulation machines". The relevant study, titled "Photochemical nanomotors reverse anxiety and depressive-related behaviors in rodents through spatiotemporal polarity dynamics tuning", was published in Nature Communications.
