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Fluorophores lay the material basis for tissue labeling and fluorescence imaging, especially for deep‐brain multiphoton microscopy (MPM) in animal models. Among various fluorescent materials, those with aggregation‐induced emission (AIE) characteristics, i.e., AIEgens, have excellent optical properties and biocompatibility and thus have found widespread applications in biomedical imaging. However, their application to deep‐brain MPM has so far been limited in imaging depth, which undoubtedly poses a hindrance to neurological research aiming to probe the deeper brain. In order to address the issue, here a novel bright AIEgen, namely MTTCM, is designed and synthesized via facile reactions routes. The self‐assembled MTTCM nanoparticles (NPs) with their water‐dispersible feature, have good biocompatibility and good photostability. Furthermore, they are spectrally advantageous for deep‐brain MPM: their emission lies in the NIR‐I region, they generate 3‐photon fluorescence with NIR‐III excitation and show only a slight blue‐shift in the emitted 3‐photon fluorescence in vivo. From a fundamental photochemical perspective, it is also confrimed that MTTCM NPs obey Kasha's rule since the measured 3‐photon and 1‐photon fluorescence spectra overlap. All these merits make MTTCM NPs the enabling fluorophores for record depth in brain imaging in vivo: 1905 µm after craniotomy and 1100 µm through an intact skull, excited at 1660 nm. Furthermore, a record 752 µm hemodynamic imaging depth before craniotomy is demonstrated, from which the blood flow speed can be measured. MTTCM NPs are thus promising fluorophores for deep‐brain 3‐photon imaging in vivo. [ABSTRACT FROM AUTHOR]

Optical nanoscale technologies often implement covalent or noncovalent strategies for the modification of nanoparticles, whereby both functionalizations are leveraged for multimodal applications but can affect the intrinsic fluorescence of nanoparticles. Specifically, single‐walled carbon nanotubes (SWCNTs) can enable real‐time imaging and cellular delivery; however, the introduction of covalent SWCNT sidewall functionalizations often attenuates SWCNT fluorescence. Recent advances in SWCNT covalent functionalization chemistries preserve the SWCNT's pristine graphitic lattice and intrinsic fluorescence, and here, such covalently functionalized SWCNTs maintain intrinsic fluorescence‐based molecular recognition of neurotransmitter and protein analytes. The covalently modified SWCNT nanosensor preserves its fluorescence response towards its analyte for certain nanosensors, presumably dependent on the intermolecular interactions between SWCNTs or the steric hindrance introduced by the covalent functionalization that hinders noncovalent interactions with the SWCNT surface. These SWCNT nanosensors are further functionalized via their covalent handles with a targeting ligand, biotin, to self‐assemble on passivated microscopy slides, and these dual‐functionalized SWCNT materials are explored for future use in multiplexed sensing and imaging applications. [ABSTRACT FROM AUTHOR]

Abstract: Deliberate design of specific and sensitive molecular probes with distinctive physical/chemical properties for analyte sensing is of great significance. Herein, by taking advantage of the position‐dependent substituent effects, an aggregation‐induced emission featured iron (III) probe from ortho‐substituted pyridinyl‐functionalized tetraphenylethylene (TPE‐o‐Py) is synthesized. It displays high sensitivity and selectivity toward iron (III) detection. The recognition arises from the position isomer of ortho‐substitution, and the fact that TPE‐o‐Py has a low acid dissociation constant (pK a) that is close to that of hydrolyzed Fe3+. Importantly, TPE‐o‐Py as a light‐up fluorescence probe could be employed for Fe3+ sensing in living cells with a pronounced red‐shift in fluorescence emission. [ABSTRACT FROM AUTHOR]

Red/near-infrared (NIR) fluorescent molecules with aggregation-induced emission (AIE) characteristics are of great interest in bioimaging and therapeutic applications. However, their complicated synthetic approaches remain the major barrier to implementing these applications. Herein, a one-pot synthetic strategy to prepare a series of red/NIR-emissive AIE luminogens (AIEgens) by fine-tuning their molecular structures and substituents is reported. The obtained AIEgens possess simple structures, good solubilities, large Stokes shifts, and bright emissions, which enable their applications toward in vitro and in vivo imaging without any pre-encapsulation or -modification steps. Excellent targeting specificities to lipid droplets (LDs), remarkable photostabilities, high brightness, and low working concentrations in cell imaging application make them remarkably impressive and superior to commercially available LD-specific dyes. Interestingly, these AIEgens can efficiently generate reactive oxygen species upon visible light irradiation, endowing their effective application for photodynamic ablation of cancer cells. This study, thus, not only demonstrates a facile synthesis of red/NIR AIEgens for dual applications in simultaneous imaging and therapy, but also offers an ideal architecture for the construction of AIEgens with long emission wavelengths. [ABSTRACT FROM AUTHOR]

Ester, amide, and directly linked composites of squalene and cationic diaza [4]helicenes 1 are readily prepared. These lipid-dye constructs 2, 3, and 4 give in aqueous media monodispersed spherical nanoassemblies around 100-130 nm in diameter with excellent stability for several months. Racemic and enantiopure nanoassemblies of compound 2 are fully characterized, including by transmission electron microscope and cryogenic transmission electron microscope imaging that did not reveal higher order supramolecular structures. Investigations of their (chir)optical properties show red absorption maxima ≈600 nm and red fluorescence spanning up to the near-infrared region, with average Stokes shifts of 1350-1550 cm−1. Live-cell imaging by confocal microscopy reveals rapid internalization on the minute time scale and organelle-specific accumulation. Colocalization with MitoTracker in several cancer cell lines demonstrates a specific staining of mitochondria by the [4]helicene-squalene nanoassemblies. To our knowledge, it is the first report of a subcellular targeting by squalene-based nanoassemblies. [ABSTRACT FROM AUTHOR]