Illuminating Cell Signaling with Near-Infrared Light-Responsive Nanomaterials

Abstract

The regulation of cellular signaling in vivo has been a challenging task owing to the lack of effective methods for tunable control of the amplitude, location, and duration of cell-signaling events at a deep-tissue level. In this issue of ACS Nano, an intriguing paper by Ambrosone et al. demonstrates that deep-tissue-penetrating near-infrared (NIR) light can be used to control the Wnt/β-catenin-signaling pathway in a single-cell organism (Hydra) by utilizing microcapsules that contain plasmonic gold nanoparticles. In parallel, in recent work, we proposed upconversion nanoparticles (UCNPs) as NIR-light-activatable “wireless” optogenetic tools, and we showed their ability to modulate cell signaling pathways in both mammalian cells and mice. We believe that these interesting NIR-light-responsive nanotechnologies will open new avenues for both basic research and clinical applications.

Optogenetic Immunomodulation: Shedding Light on Antitumor Immunity

“…In addition to its best-established role in driving T lymphocyte activation, intracellular Ca 2+ mobilization promotes inflammasome activation in macrophages, DC maturation, and antigen presentation [17–19]. By mimicking a conformational switch in STIM1 [18, 20] and thus obviating the need for physiological stimulus or store depletion to elicit Ca 2+ entry, He et al developed an Opto-CRAC system (Figure 1b) to photo-trigger Ca 2+ influx and faithfully phenocopy hallmark Ca 2+ -dependent responses in immune cells following light stimulation [21, 22]. When introduced into therapeutic DCs in a mouse model of melanoma, engineered Opto-CRAC channels function as “photoactivatable adjuvants” to enhance DC maturation and antigen presentation (step 1; Figure 1a), thereby promoting T cell priming and activation (step 2) to facilitate the killing of melanoma and its metastases at distal sites [21].…”

“…This unique feature has been exploited to induce local protein oligomerization to activate Ca 2+ influx [57], Wnt signaling [22, 52], and GTPases [52] or receptor tyrosine kinases [53, 56, 58]. Compared with the optical dimerizers described above, optogenetic applications with this strategy only need a single construct.…”

“…Lanthanide-doped upconversion nanoparticles (UCNPs) are capable of producing anti-Stokes luminescence by converting NIR light into shorter wavelength emissions, with additional advantages of reduced tissue scattering and phototoxicity (Figure 3b) [22, 67, 68]. UCNPs shift the light-harvesting window to the NIR region, where deep tissue penetration and remote stimulation are feasible.…”

Imaging Nanotherapeutics in Inflamed Vasculature by Intravital Microscopy

“…Nanomedicines are conceptually defined as nanotechnology applications in medicine including biosensing1, diagnostics2, 3, imaging4, 5 and targeted drug delivery4, 6-9. Targeted drug delivery using nanoparticles could dramatically increase therapeutic efficacy and avoid the systemic toxicity 10, 11.…”

Designed Er^3+-singly doped NaYF_4 with double excitation bands for simultaneous deep macroscopic and microscopic upconverting bioimaging

“…All these applications benefit from the distinguished merits of UCNPs, including tunable excitation, narrow band emissions, large anti-Stokes shifts, long lifetimes, superior stability, low toxicity, weak fluorescence background [11][12][13][14]. In addition, the absorption range of UCNPs can be broadened and the upconversion efficiency can be boosted using NIR dye-sensitized UCNPs [15][16][17][18]. Superior to other kinds of fluophores, UCNPs has the unique property of multiple excitation bands and holds the potential to achieve simultaneous deep microscopic and macroscopic upconversion imaging.…”