General and Scalable Approach to Bright, Stable, and Functional AIE Fluorogen Colloidal Nanocrystals for in Vivo Imaging

Abstract

Fluorescent nanoparticles built from aggregation-induced emission-active organic molecules (AIE-FONs) have emerged as powerful tools in life science research for in vivo bioimaging of organs, biosensing, and therapy. However, the practical use of such biotracers has been hindered owing to the difficulty of designing bright nanoparticles with controlled dimensions (typically below 200 nm), narrow size dispersity and long shelf stability. In this article, we present a very simple yet effective approach to produce monodisperse sub-200 nm AIE fluorescent organic solid dispersions with excellent redispersibility and colloidal stability in aqueous medium by combination of nanoprecipitation and freeze-drying procedures. By selecting polymer additives that simultaneously act as stabilizers, promoters of amorphous-crystalline transition, and functionalization/cross-linking platforms, we demonstrate a straightforward access to stable nanocrystalline FONs that exhibit significantly higher brightness than their amorphous precursors and constitute efficient probes for in vivo imaging of the normal and tumor vasculature. FONs design principles reported here are universal, applicable to a range of fluorophores with different chemical structures and crystallization abilities, and are suitable for high-throughput production and manufacturing of functional imaging probes.

Push–Pull Dyes for Yellow to NIR Emitting Electrochemical Cells

“…Dyes with a large angle sum (A πD plus A πA ) form distorted structures projected from the central π-bridge. These distorted structures were confirmed by the single crystal X-ray diffraction (XRD) data [31,33,37] of dyes I-III and V, which show larger A πD than A πA that matched well to the calculated results (Table S3, Supporting Information). The interchromophore dye-dye stacking distance increased in the order I < II < V << III ( Figure S7, Supporting Information).…”

“…[34,35] The Onsager radii were estimated from Suppan's equation [36] (see the Supporting Information) using the density obtained from X-ray diffraction on single crystals. [31,33,37] From those Onsager radii (Table S2, Supporting Information), dipole moment variations from 16-19.1 (I-IV) to 9.6 D (V) were determined. Thus, the dipole moment increase upon excitation of dyes I-IV is approximately twice as strong as that of dye V. Finally, it is interesting to note that all dyes present large Stokes shifts (5000-7500 cm −1 ), also characteristic of their strong intramolecular CT, so low autoabsorption can be expected in the films.…”

Use of Nanoparticles in Tissue Engineering and Regenerative Medicine

“…Among different diagnostic tools, imaging can visualize diseased tissues, tissue healing and stem cell fate through providing contrast with respect to other tissues or by labeling NPs with an appropriate ligand. Fluorescent labeling, single photon emission computerized tomography (SPECT), ultrasound, MRI, NIR fluorescence imaging are among the widely used imaging techniques which alone or in conjugation with each other can provide sensitive, high resolution images from tissues through utilization of contrast agents (Harrison et al, 2014; Hong et al, 2014; Gu et al, 2017; Savla and Minko, 2017; Ekkelenkamp et al, 2018; Yan et al, 2018). Direct injection of contrast agents has poor outcomes due to short half-life, degradation, low concentration in desired tissue and toxicity at high dosages.…”

Biologically Excretable Aggregation‐Induced Emission Dots for Visualizing Through the Marmosets Intravitally: Horizons in Future Clinical Nanomedicine

“…The AIEgens were then encapsulated into organic nanoparticles by nanoprecipitation, [22] using US Food and Drug Administration (FDA)-approved F-127 (Figure 1D). The amphiphilic block copolymers could ameliorate the hydrophilicity and biocompatibility of luminescent probes.…”