Aggregation-Induced Emission Luminogen with Near-Infrared-II Excitation and Near-Infrared-I Emission for Ultradeep Intravital Two-Photon Microscopy

Abstract

Currently, a serious problem obstructing the large-scale clinical applications of fluorescence technique is the shallow penetration depth. Two-photon fluorescence microscopic imaging with excitation in the longer-wavelength near-infrared (NIR) region (>1100 nm) and emission in the NIR-I region (650-950 nm) is a good choice to realize deep-tissue and high-resolution imaging. Here, we report ultradeep two-photon fluorescence bioimaging with 1300 nm NIR-II excitation and NIR-I emission (peak ∼810 nm) based on a NIR aggregation-induced emission luminogen (AIEgen). The crab-shaped AIEgen possesses a planar core structure and several twisting phenyl/naphthyl rotators, affording both high fluorescence quantum yield and efficient two-photon activity. The organic AIE dots show high stability, good biocompatibility, and a large two-photon absorption cross section of 1.22 × 10 GM. Under 1300 nm NIR-II excitation, in vivo two-photon fluorescence microscopic imaging helps to reconstruct the 3D vasculature with a high spatial resolution of sub-3.5 μm beyond the white matter (>840 μm) and even to the hippocampus (>960 μm) and visualize small vessels of ∼5 μm as deep as 1065 μm in mouse brain, which is among the largest penetration depths and best spatial resolution of in vivo two-photon imaging. Rational comparison with the AIE dots manifests that two-photon imaging outperforms the one-photon mode for high-resolution deep imaging. This work will inspire more sight and insight into the development of efficient NIR fluorophores for deep-tissue biomedical imaging.

Molecular Engineering of an Organic NIR‐II Fluorophore with Aggregation‐Induced Emission Characteristics for In Vivo Imaging

“…This unique property endows AIE NPs with a relatively high quantum yield and brightness, which facilitate in vivo imaging. However, the emission spectra of AIE NPs reported to date are mainly within the visible and NIR‐I regions . Deeper tissue imaging and higher signal‐to‐background ratios require AIE NPs with NIR‐II emission.…”

Beyond 1000 nm Emission Wavelength: Recent Advances in Organic and Inorganic Emitters for Deep‐Tissue Molecular Imaging

“…h) In vivo and real‐time fluorescence microscopic imaging of mouse brain vasculature at 1065 µm with TQ‐BPM administration. Reproduced with permission . Copyright 2018, American Chemical Society.…”

“…Based on these excellent results, vascular hemodynamic could be evaluated, photothrombotic ischemia (PTI) and blood–brain barrier (BBB) damage in animal models could also be monitored with the help of TQ‐BPN . To further improve the resolution and tissue‐imaging depth, TQ‐BPN was excited by NIR‐II laser and emitted in the NIR‐I channel and achieved fluorescent 3D imaging of vasculature with sub‐3.5 µm spatial resolution and detailed brain vessels of ≈5 µm at 1065 µm depth with two‐photon fluorescence imaging (Figure h) . In order to tracing long‐term disease information, AIE‐based BPN‐BBTD was constructed to observe orthotopic bladder tumor and monitor the process of tumor diagnosis, treatment, and prognosis after photothermal therapy during a long period (Figure i) .…”

Fused pyrazole-phenanthridine based dyads: synthesis, photo-physical and theoretical studies, and live cell pH imaging

“…Yield: 65%. 1 H NMR and 13 C were recorded by dissolving compounds in CDCl 3 solvent. Chemical shis (d) are given in ppm relative to TMS internal standard.…”

“…Functional organic compounds, especially, stimuli-responsive organic emissive materials, have gained considerable attention in materials science, [1][2][3][4][5][6][7][8] medicine, 9-12 biology [13][14][15][16] and environmental analytics. [17][18][19][20][21] Among them, the acidochromic materials, whose emission response depends on the pH of the medium, have received considerable attention because they nd applications in various elds of scientic research such as environment, ecology, agriculture, and biological processes.…”