Design of Smart Aggregates: Toward Rapid Clinical Diagnosis of Hyperlipidemia in Human Blood

Abstract

of macroscopic systems, reductionism is always employed: molecules are the smallest compositive units, and a whole (system) is nothing but the sum of its individual parts (molecules). [1] And based on this approach, many scientific rules and theorems such as the Beer-Lambert law are developed through experimental data in dilute solutions to avoid the interference of intermolecular interactions. [2,3] However, the behaviors and properties of molecules will be largely changed in concentrated solutions or in their aggregate state. For example, many aromatic compounds emit intensely in dilute solutions but become weakly emissive in the aggregate state, such a phenomenon is referred to as aggregation-caused quenching. [4] On the other hand, some molecules would act differently and show enhanced light emission when aggregated, such a behavior is called aggregation-induced emission (AIE). [5] These aggregates with mesoscale are important mediators for the transfer and amplification of macroscopic properties. Therefore, the paradigm shift from reductionism to aggregation science helps the study of exploiting and regulating their new properties. [6] Molecular aggregates with environmental responsive properties are desired for their wide practical applications such as bioprobes. Here, a series of smart near-infrared (NIR) luminogens for hyperlipidemia (HLP) diagnosis is reported. The aggregates of these molecules exhibit a twisted intramolecular charge-transfer effect in aqueous media, but aggregation-induced emission in highly viscous media due to the restriction of the intramolecular motion. These aggregates, which can autonomously respond to different environments via switching the aggregation state without changing their chemical structures are described, as "smart aggregates". Intriguingly, these luminogens demonstrate NIR-II and NIR-III luminescence with ultralarge Stokes shifts (>950 nm). Both in vitro detection and in vivo imaging of HLP can be realized in a mouse model. Linear relationships exist between the emission intensity and multiple pathological parameters in blood samples of HLP patients. Thus, the design of smart aggregate facilitates rapid and accurate detection of HLP and provides a promising attempt in aggregate science.

Combination of changeable π-conjugation and hydrophilic groups for developing water-soluble small-molecule NIR-II fluorogenic probes

“…[1][2][3] In particular, the second near-infrared (NIR-II, 900-1700 nm) uorescence imaging can considerably reduce the light scattering and auto-uorescence, and thus is more suitable for in vivo analysis at deeper penetration. [4][5][6][7][8][9][10][11] There are two main types of NIR-II probes, which are based on inorganic and organic materials, respectively. Inorganic probes have long been accompanied by the controversial toxicity issue, impeding the further clinical application; whereas organic small-molecule probes display the merit of good biosafety as well as exible structure modication, and have broader prospects for bioimaging.…”

Donor–Acceptor Engineering for Tailoring Highly Efficient Photosensitizers for Image-Guided Antitumor Photodynamic Therapy

“…However, increasing water content in the THF/water mixture, the PS emission was gradually intensified. This behavior was due to the formation of nanoaggregates, restriction of molecular rotation, and prevention of the excited-state energy consumption via non-radiative pathways, a typical behavior of AIE systems . The AIE property of the PSs was also verified by quantum yield Φ F values (0.36%, 0.39%, and 0.22%) for TPA-T-RS, TPA-Ts-RS, and TPA-Ts-RCN, respectively (Figures S21 and S22).…”

Fluorescent Probes for Disease Diagnosis

“…Further adding to an already significant body of work in the field, in 2022 the Tang group reported a series of intelligent NIR fluorophores for the diagnosis of hyperlipidemia (Figure , probes 145 ) . As they are based on a molecular rotor donor–zwitterionic unit acceptor template, they exhibit twisted ICT properties, and so have minimal fluorescence in aqueous environments, but emit strongly on aggregation in highly viscous media.…”