Strategies to Overcome the Limitations of AIEgens in Biomedical Applications

Abstract

NPs), [7][8][9][10] fluorescent proteins (FPs), [11,12] conjugated polymer NPs, [13] dye-loaded polymer NPs, [14] and lipid NPs [15] have been exploited in biomedical applications. QDs have bright fluorescence and are generally photostable under various biological conditions. To date, it is well understood that their toxicity is a major concern for translating them for clinical research. [16,17] It is also worth noting that many surfactants used currently for the synthesis of inorganic or organic NPs, e.g., sodium dodecyl sulfate and cetyltrimethylammonium bromide, [18,19] are highly toxic, and leftover surfactants deposited on these NPs may cause harmful effects to the living system. FPs are promising optical probe candidates for bioimaging due to their inherent biocompatibility and ability to be functionalized with ligands for targeted delivery. However, they require complicated transfection process in practical applications. The widely used conventional luminophores have suffered from the notorious aggregation-caused quenching (ACQ) effect, [20,21] which results in decreased or completely quenched fluorescence when they are formulated into NPs. Both dye-doped NPs and π-conjugated polymer NPs have been applied in a wide range of applications, such as fluorescence imaging and biosensing due to their distinct characteristics such as tunable emission wavelength, fast emission rate, excellent photostability, etc. However, most of these systems suffer from ACQ issue, which restricts the loading of optically active materials into the NPs. Recently, great efforts have been made to address the ACQ issue. Fluorophores are usually modified with bulky side chains to minimize the strong π-stacking. This strategy is generally associated with blueshifted fluorescence, which is undesirable for imaging applications. Recently, Klymchenko and co-workers proposed a new concept for preparing fluorescent polymer NPs. These NPs were doped with ionic-liquid-like salts of a cationic dye with a bulky hydrophobic counterion that serves as spacer for minimizing dye aggregation and self-quenching; [22] the synthesized NPs were loaded with 500 dye molecules and they were much brighter than QDs.In 2001, Tang and co-workers coined the concept of aggregation-induced emission (AIE), wherein some fluorogens have shown extremely weak emission in molecular states but highly bright emission in the aggregate or solid states. [23] Fluorogens with AIE characteristics (AIEgens) normally possess rotor-like Motivated by the demand for high-performance tools for biomedical applications, numerous new luminescent nanomaterials with advanced functionalities are synthesized in recent years. Conventional fluorophores generally suffer from the notorious aggregation-caused quenching effect that deteriorates their practical performance. The recently emerged fluorogens with aggregation-induced emission (AIE) characteristics (AIEgen) have generated a new avenue for biomedical applications due to their unique optical properties, flexible designability, and multifun...

Add the Finishing Touch: Molecular Engineering of Conjugated Small Molecule for High‐Performance AIE Luminogen in Multimodal Phototheranostics

“…[ 11,12 ] Given the circumstances, emerging research interest is the aggregation‐induced emission (AIE), which refers to a photophysical phenomenon wherein a novel family of propeller‐shaped luminogens with twisted structural conformation are weakly emissive or nonemissive in the single‐molecule state, but are induced to emit intensely in the aggregates through a mechanism of the restriction of intramolecular motions (RIM). [ 13–23 ] AIE luminogens (AIEgens) have triggered state‐of‐the‐art developments in FLI, thanks to their intrinsic properties including high signal‐to‐noise ratio and high photostability. In addition, recent advances have demonstrated that AIEgens can also serve as phototheranostic agents for multimodal imaging‐guided synergistic therapy through rational molecular design, benefiting from the inherent capabilities of AIEgens as an extraordinary template for subtly regulating the balance between radiative and nonradiative decays.…”

“…[11,12] Given the circumstances, emerging research interest is the aggregation-induced emission (AIE), which refers to a photophysical phenomenon wherein a novel family of propeller-shaped luminogens with twisted structural conformation are weakly emissive or nonemissive in the single-molecule state, but are induced to emit intensely in the aggregates through a mechanism of the restriction of intramolecular motions (RIM). [13][14][15][16][17][18][19][20][21][22][23] AIE luminogens (AIEgens) have triggered state-ofthe-art developments in FLI, thanks to their intrinsic properties including high signal-to-noise ratio and high photostability.…”

Recent Advances in Aggregation‐Induced Electrochemiluminescence

“…Through long‐term mechanistic investigations of structure–property relationships, it has come to light that the restriction of intermolecular rotations and twisted intramolecular charge transfer (TICT) contribute to enhanced emission quantum yield, accompanied by prevention of excimers, formation of aggregates, and intermolecular charge transfer . To date, thousands of papers have bloomed in this hot area of AIE and hundreds of reviews have summarized various applications, such as in polymer chemistry, biovisualization, photodynamic therapy, and OLEDs . Additionally, it is AIE that could produce impressive electrochemiluminescence (abbreviated as ECL, also called electrogenerated chemiluminescence).…”

Zwitterionic Stealth Dye-Loaded Polymer Nanoparticles for Intracellular Imaging

“…In particular, dye-loaded polymer NPs have recently achieved very high brightness equivalent to 100-1000 organic dyes. [9][10][11] Achieving such high brightness required the development of new strategies to overcome aggregation-caused quenching of the fluorophores encapsulated at very high concentrations in the polymer matrix of NPs. This was achieved, for example, by using fluorophores that undergo aggregation-induced emission 12 or by using salts of fluorophores with hydrophobic bulky counterions to prevent aggregation.…”