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Mechanochemically Coupled Multidimensional Modulation of Calcium Overload
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DOI：10.1021/acsnano.6c10419.png)
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Abstract
En 中文
Disruption of calcium ion (Ca2+) homeostasis has emerged as a promising strategy for tumor therapy. However, the intricate regulation of Ca2+ signaling and the limitations of single-dimensional modulation often hinder therapeutic efficacy. Here, we developed a Janus nanomotor platform that orchestrates mechanochemically coupled multidimensional modulation of Ca2+ overload for enhanced tumor therapy. Utilizing a liquid–nano–liquid interface-mediated anisotropic encapsulation strategy, amorphous calcium carbonate (ACC) nanoparticles were asymmetrically coated with mesoporous polydopamine (mPDA) and subsequently functionalized with l-arginine (l-Arg) and hyaluronic acid (HA), forming the Janus ACC@SiO2&mPDA-Arg-HA nanomotors that combine structural asymmetry, NO-driven propulsion, and tumor-targeting capability. Within the tumor microenvironment (TME), degradation of the ACC provided a sustained exogenous Ca2+ reservoir. Simultaneously, the endogenous catalytic conversion of l-Arg into NO triggered self-propulsion, mechanically stimulating the cell membrane to activate Piezo1 channels and promote extracellular Ca2+ influx. In parallel, NO acted as a gaseous chemical messenger to trigger ryanodine receptors (RyRs)-mediated Ca2+ release from the endoplasmic reticulum (ER). The mechanically and chemically coupled regulation induces persistent Ca2+ overload, leading to mitochondrial dysfunction and apoptosis. Our study presents a paradigm of mechanochemical coupling for multidimensional signal modulation, offering a framework for engineering nanomachines that reprogram intracellular signaling in cancer therapy.
Keywords:
Calcium
Cancer therapy
Cell signaling
Nanoparticles
Tumors
Janus nanomotors
nitric oxide
calcium overload
mechanochemical coupling
cancer therapy
Journal
IF:
16
Papers:
2.6W
Citations:
25.6W
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