NIR‐II‐Excited Intravital Two‐Photon Microscopy Distinguishes Deep Cerebral and Tumor Vasculatures with an Ultrabright NIR‐I AIE Luminogen

Abstract

Intravital fluorescence imaging of vasculature morphology and dynamics in the brain and in tumors with large penetration depth and high signal‐to‐background ratio (SBR) is highly desirable for the study and theranostics of vascular‐related diseases and cancers. Herein, a highly bright fluorophore (BTPETQ) with long‐wavelength absorption and aggregation‐induced near‐infrared (NIR) emission (maximum at ≈700 nm) is designed for intravital two‐photon fluorescence (2PF) imaging of a mouse brain and tumor vasculatures under NIR‐II light (1200 nm) excitation. BTPETQ dots fabricated via nanoprecipitation show uniform size of around 42 nm and a high quantum yield of 19 ± 1% in aqueous media. The 2PF imaging of the mouse brain vasculatures labeled by BTPETQ dots reveals a 3D blood vessel network with an ultradeep depth of 924 µm. In addition, BTPETQ dots show enhanced 2PF in tumor vasculatures due to their unique leaky structures, which facilitates the differentiation of normal blood vessels from tumor vessels with high SBR in deep tumor tissues. Moreover, the extravasation and accumulation of BTPETQ dots in deep tumor (more than 900 µm) is visualized under NIR‐II excitation. This study highlights the importance of developing NIR‐II light excitable efficient NIR fluorophores for in vivo deep tissue and high contrast tumor imaging.

AIE-active two-photon fluorescent nanoprobe with NIR-II light excitability for highly efficient deep brain vasculature imaging

“…Also, the line intensity profile across a tiny blood vessel at penetration depth of 800 μm was plotted to evaluate the spatial resolution, which revealed the full width at half maximum (FWHM) to be around 1.92 μm ( Figure S36 , Supporting Information ). This very high spatial resolution made AIETP NPs an outstanding choice for brain imaging wherein the obtained resolution is much better compared to several other recently reported probes 5 , 40 - 43 . Some recently reported multi-photon fluorescent probes have been summarized in Table S1 ( Supporting Information ) to compare their imaging efficacy with that of the newly developed fluorescent probe AIETP NPs in terms of penetration depth and spatial resolution.…”

Aggregation-Induced Fluorogens in Bio-Detection, Tumor Imaging, and Therapy: A Review

“…31,87 The Vascular imaging in tumor has gained as much consideration as solid tumor imaging. 88 In general, the vascular networks play a mighty role in regulating the delivery of nutrients and oxygen supply; meanwhile, in tumor the vascular network allows the cancer cells to disseminate and influences the response of the tumor cells to therapy. 89 Tumor vascular networks are typically sinusoidal, exhibit discontinuous basement membranes and lack tight endothelial cell junctions making them highly permeable.…”

Nanomaterials with Supramolecular Assembly Based on AIE Luminogens for Theranostic Applications

“…Liu's group designed and synthesized a NIR-II fluorophore, that is, BTPETQ with aggregation-induced NIR emission at 700 nm and long-wavelength absorption. [77] BTPETQ dots were constructed further via nanoprecipitation and incorporation with DSPE-PEG. BTPETQ dots exhibited ultrabright, two-photon, and aggregation-induced NIR emission, enabling illumination and distinction of deep cerebral and tumor vasculatures under NIR-II light excitation.…”