Ultrafast Near‐Infrared Light‐Triggered Intracellular Uncaging to Probe Cell Signaling

Abstract

The possibility of regulating cell signaling with high spatial and temporal resolution within individual cells and complex cellular networks has important implications in biomedicine. In this report, we demonstrate a general strategy that uses near-infrared tissue-penetrating laser pulses to uncage biomolecules from plasmonic gold-coated liposomes, i.e. plasmonic liposomes, to activate cell signaling in a non-thermal, ultrafast and highly controllable fashion. Near-infrared picosecond laser pulse induces transient nanobubbles around plasmonic liposomes. The mechanical force generated from the collapse of nanobubbles rapidly ejects encapsulated compound within 0.1 ms. We showed that single pulse irradiation triggers the rapid intracellular uncaging of calcein from plasmonic liposomes inside endo-lysosomes. The uncaged calcein then evenly distributes over the entire cytosol and nucleus. Furthermore, we demonstrated the ability to trigger calcium signaling in both an immortalized cell line and primary dorsal root ganglion (DRG) neurons by intracellular uncaging of inositol triphosphate (IP3), an endogenous cell calcium signaling second messenger. Compared with other uncaging techniques, this ultrafast near-infrared light-driven molecular uncaging method is easily adaptable to deliver a wide range of bioactive molecules with an ultrafast optical switch, enabling new possibilities to investigate signaling pathways within individual cells and cellular networks.

Overcoming Multidrug Resistance by On-Demand Intracellular Release of Doxorubicin and Verapamil

“…Transmission electron microscopy (TEM) observation showed that gold nanoparticles were distributed on the surface (Figure 1(a)). The structure of gold liposomes we observed was similar to the previously reported gold liposomes prepared by the same method [22]. UV-Vis spectra of gold liposomes exhibited an absorption peak at around 650 nm, while uncoated liposomes did not show any resonance peak in the wavelength range of 400-800 nm (Figure 2(b)).…”

“…This technique enables intracellular release of trapped therapeutic agents and is promising for enhancing the therapeutic effects. In a previous report, picosecond-pulsed laser-triggered cargo release from gold liposomes has been used to manipulate cell signaling [22]. We believe that our technique may also find many other biological applications where intracellular cargo release is required.…”

Understanding the Collective Optical Properties of Complex Plasmonic Vesicles

“…Researchers have demonstrated that plasmonic vesicles can enable ultraviolet (UV) or near‐infrared (NIR) light‐induced cargo release . Our recent studies demonstrates the feasibility of nonthermal, ultrafast and highly controllable uncaging of biomolecules from plasmonic gold‐coated liposomes by NIR laser pulses …”

“…Understanding plasmonic interactions in complex nanostructures is key to further design nanosystems for biomedical applications . Plasmonic gold‐coated liposomes exhibit a characteristic NIR peak by depositing 3–5 nm gold nanoparticles on the liposome surface . Self‐assembled vesicles using polymer‐tethered gold nanoparticles (typically > 15 nm) show a range of optical properties including absorption peak in the visible and NIR ranges or broad absorption spectrum, depending on the nanoparticle assembly density ( Figure ) .…”

“…B) TEM image of gold nanoparticle‐coated liposome. Reproduced with permission . Copyright 2017, John Wiley and Sons.…”