Near-Infrared Light-Activated DNA-Agonist Nanodevice for Nongenetically and Remotely Controlled Cellular Signaling and Behaviors in Live Animals

Abstract

Optogenetics provides promising tools for the precise control of receptor-mediated cell behaviors in a spatiotemporal manner. Most photoreceptors, yet, require extensive genetic manipulation and respond only to ultraviolet or visible light, which are suboptimal for in vivo applications because they do not penetrate thick tissues. Here we report a novel near-infrared light-activated DNA agonist (NIR-DA) nanodevice for nongenetic manipulation of cell signaling and phenotype in deep tissues. This nanodevice is prepared by conjugating a pre-inactivated DNA agonist onto the gold nanorods (AuNRs). Upon NIR light treatment, the DNA agonist is released through the localized surface plasmon resonance (LSPR)-based photothermal effect of AuNRs and becomes active. The active DNA agonist dimerizes the DNA-modified chimeric or native receptor tyrosine kinase (RTK) on cell surfaces and activates downstream signal transduction in live cells. Such NIR-DA activation of RTK signaling enables the control of cytoskeletal remodeling, cell polarization, and directional migration. Furthermore, we demonstrate that the NIR-DA system can be used in vivo to mediate RTK signaling and skeletal muscle satellite cell migration and myogenesis, which are critical cellular behaviors in the process of skeletal muscle regeneration. Thus, the NIR-DA system offers a powerful and versatile platform for exogenous modulation of deep tissues for purposes such as regenerative medicine.

Nucleic acid constructs for the interrogation of multivalent protein interactions

“…15D). 52 As the gold nanorods (B60 nm long, B14 nm wide) absorbed near-IR light and converted the energy into heat, the attached DNA agonists were released into solution where they could bridge two receptor-bound DNA aptamers. Roughly half of the B200 nanorod-bound DNA agonists could be deployed within 4 minutes of irradiation using an 808 nm laser.…”

Advanced Near‐Infrared Light for Monitoring and Modulating the Spatiotemporal Dynamics of Cell Functions in Living Systems

“…[ 49,50 ] Thereby, a series of temperature‐dependent biological processes can be modulated by the generated heat, such as photothermal cell killing, heat‐related gene expression, heat‐controlled drug release, and photothermal neuron activation. [ 49,51,52,27 ] Third, NIR light can be used to generate reactive oxygen species (ROS) via the photosensitizer‐based nanomaterials, thus being widely used in photodynamic therapy (PDT) of cancer. [ 26,53 ] Fourth, NIR light also can be used to modulate electron transfer in cells via the photoelectrochemical nanomaterials (such as silicon‐based nanostructured materials), thus being used for optical neuromodulation and stem cell‐based regenerative medicine.…”

Engineering Cell‐Surface Receptors with DNA Nanotechnology for Cell Manipulation

“…However, this system requires ultraviolet light, which has narrow tissue penetration and potential phototoxicity, both of which limit potential in vivo application. To solve this problem, our group proposed a NIR‐activated DNA agonist (NIR‐DA) nanodevice for non‐genetic regulation of cell behavior in vivo (Figure D) . An RTK‐activating DNA dimer was functionalized on AuNRs (a NIR‐responsive nanomaterial), as a latent agonist complex, enabling NIR‐triggered release and activation of DNA agonist through the local‐surface‐plasmon‐resonance (LSPR)‐based photothermal effect.…”

“…To solve this problem, our group proposed aN IR-activated DNA agonist (NIR-DA) nanodevice for non-genetic regulation of cell behavior in vivo ( Figure 4D). [65] An RTK-activating DNA dimer was functionalized on AuNRs( aN IR-responsive nanomaterial), as al atent agonist complex, enabling NIR-triggered releasea nd activation of DNA agonistt hrough the local-surface-plasmon-resonance (LSPR)based photothermal effect.T he activated DNA agonists dimerized the RTKs on the cell surfaces and promoted cell migration. The in vivo applicationo ft hese NIR-DA nanodevicesd emonstrated that NIR light accelerated the migration andd ifferentiation of skeletal muscle satellite cells at injureds ites in mice, promoting the skeletal muscle regenerative progress.…”