Shiqin Zhu

Far‐Red and Near‐IR AIE‐Active Fluorescent Organic Nanoprobes with Enhanced Tumor‐Targeting Efficacy: Shape‐Specific Effects

The rational design of high-performance fluorescent materials for cancer targeting in vivo is still challenging. A unique molecular design strategy is presented that involves tailoring aggregation-induced emission (AIE)-active organic molecules to realize preferable far-red and NIR fluorescence, well-controlled morphology (from rod-like to spherical), and also tumor-targeted bioimaging. The shape-tailored organic quinoline-malononitrile (QM) nanoprobes are biocompatible and highly desirable for cell-tracking applications. Impressively, the spherical shape of QM-5 nanoaggregates exhibits excellent tumor-targeted bioimaging performance after intravenously injection into mice, but not the rod-like aggregates of QM-2.

Insight into aggregation-induced emission characteristics of red-emissive quinoline-malononitrile by cell tracking and real-time trypsin detection

Water-soluble, long wavelength fluorescent aggregation-induced emission (AIE)-active materials are in great demand for high contrast biosensing and bioimaging. The substitution position effects of the sulfonate group on the basis of two quinoline-malononitrile (QM) derivatives (EDS and EDPS) provide insight into efficient modulation in the hydrophilicity, emitting color, and specific AIE characteristics. EDS shows a unique AIE behaviour in aqueous solution, but EDPS does not. The abnormal non-fluorescence aggregation for EDS in pure water is capsule-like with loose packing characteristics, but still has enough cavities or free volume to consume the radiative energy, resulting in nearly no fluorescence. When binding with the protein BSA, the sulfonate unit as a conformation function group (CFG) plays a vital role in altering its initial loose ensemble into tightly compact aggregation with light-up AIE characteristics. By cell tracking, dynamic light scattering (DLS) and transmission electron microscopy (TEM), the key role of sulfonate groups in the conformation alteration has been well demonstrated for the first time. Moreover, EDS is successfully exploited in a label-free real time AIE fluorescent assay for trypsin detection and inhibitor screening. The hydrophilic sulfonate group from the different substitution position in the AIE-active QM building blocks provides an effective way to tailor the intermolecular aggregation associated with molecular stacking, especially for in situ cell tracking and real-time trypsin detection.

A Multiaddressable Photochromic Bisthienylethene with Sequence-Dependent Responses: Construction of an INHIBIT Logic Gate and a Keypad Lock

A photochromic bisthienylethene derivative (BIT) containing two imidazole units has been synthesized and fully characterized. When triggered by chemical ions (Ag(+)), protons, and light, BIT can behave as an absorbance switch, leading to a multiaddressable system. BIT exhibits sequence-dependent responses via efficient interaction of the specific imidazole unit with protons and Ag(+). Furthermore, an INHIBIT logic gate and a keypad lock with three inputs are constructed with the unimolecular platform by employing an absorption mode at different wavelengths as outputs on the basis of an appropriate combination of chemical and photonic stimuli.

Near-Infrared Colorimetric and Fluorescent Cu2+ Sensors Based on Indoline–Benzothiadiazole Derivatives via Formation of Radical Cations

The donor-acceptor system of indoline-benzothiadiazole is established as the novel and reactive platform for generating amine radical cations with the interaction of Cu(2+), which has been successfully exploited as the building block to be highly sensitive and selective near infrared (NIR) colorimetric and fluorescent Cu(2+) sensors. Upon the addition of Cu(2+), an instantaneous red shift of absorption spectra as well as the quenched NIR fluorescence of the substrates is observed. The feasibility and validity of the radical cation generation are confirmed by cyclic voltammetry and electron paramagnetic resonance spectra. Moreover, the introduction of an aldehyde group extends the electron spin density and changes the charge distribution. Our system demonstrates the large scope and diversity in terms of activation mechanism, response time, and property control in the design of Cu(2+) sensors.

Rational design of a turn-on fluorescent sensor for α-ketoglutaric acid in a microfluidic chip

Detection of biomarkers via optical microfluidic chips is in great demand for high contrast biosensing and bioimaging. In distinct contrast with traditional chromatographic methods, which require tedious pretreatment and are not directly applicable in blood serum, a “turn-on” fluorescent sensor for the cancer cell damaging agent α-ketoglutaric acid (α-KA) has been established. A hydrazino group is introduced into the naphthalimide moiety as the reaction trigger for the specific fluorescence turn-on response. Under the rational design, probe 3 can successfully detect α-KA in a purely aqueous system, along with approximately 7-fold fluorescence enhancement and a rapid response with the aid of micelles. The sensor exhibits good selectivity among 20 common amino acids, in particular showing little interference with various dicarbonyl derivatives and reactive oxygen species. Finally, the detection of α-KA in human serum is demonstrated in a microfluidic chip, indicative of a potential platform for high-throughput screening and monitoring of kinetics, especially in biological fields.

A novel colorimetric and ratiometric NIR fluorescent sensor for glutathione based on dicyanomethylene-4 H -pyran in living cells

Glutathione (GSH) plays a critical role in maintaining oxidation-reduction homeostasis in biological systems. Considering the detection of GSH by fluorescence sensors is limited by either the short wavelength emission or the poor photostability, a highly stable colorimetric and ratiometric NIR fluorescent sensor (DCM-S) for GSH detection has been constructed on the basis of dicyanomethylene-4H-pyran (DCM) chromophore. The specific disulfide bond is incorporated via a carbamate linker as the GSH responsive group, which simultaneously blue-shifts and quenches the fluorescence. Upon addition of GSH, DCM-S exhibits outstanding colorimetric (from yellow to red) and ratiometric fluorescent response with the 6-fold enhancement of NIR fluorescence at 665 nm in quantum yield. More importantly, the GSH-treated DCM-S (DCM-NH2 actually) possesses 20-fold longer fluorescence half-life period as well as much better photostability than the FDA-approved ICG. Finally, the ratiometric detection of GSH is also successfully operated in the living cell imaging, exhibiting NIR fluorescence and large Stokes shift (215 nm) with nearly no background fluorescence interference. As a consequence, DCM-S can be utilized as colorimetric and ratiometric NIR fluorescent sensor for GSH, with a great potential in the development of GSH-induced drug delivery system.

Rational design of novel near-infrared fluorescent DCM derivatives and their application in bioimaging

The development of innovative strategies for high-performance near-infrared (NIR) fluorescent materials is in urgent demand for bioimaging. By replacing the stronger electron-withdrawing groups or extending the π-conjugated system, novel NIR fluorescent materials of DCM analogues have been developed, along with several striking characteristics: bright NIR fluorescence over 700 nm, large Stokes shift and good photo-stability. It is demonstrated that introducing a stronger electron-withdrawing unit to the acceptor moiety of DCM analogues is a favourably efficient strategy to tune and prolong the emission wavelength into the NIR region with a large Stokes shift. In comparison with the commercial NIR dye ICG, S-DCM-N and S-DCM-P display excellent photostability and low photobleaching. The large Stokes Shift and NIR fluorescence channel of S-DCM-N and S-DCM-P are very favourable for fluorescence labelling with a high signal-to-noise ratio in living species.

Near-Infrared Fluorescent Theranostic Cisplatin Prodrug with Transcatheter Intra-Arterial Therapy: Application to Rabbit Hepatocellular Carcinoma

Transcatheter intra‐arterial therapy (TIT) has become valuable in the battle against primary and secondary hepatic malignancies. However, the lack of a mechanism to visualize real‐time drug release and avoid fast metabolic clearance of chemotherapeutic agents is the primary barrier to TIT for hepatocellular carcinoma. Here, a specific near‐infrared (NIR) fluorescent prodrug platform, that is, DSPE‐mPEG/DCM‐S‐Pt micelles (DCM‐S‐Pt@PEG), to assist TIT in direct administration to large mammals like rabbits, is presented. DCM‐S‐Pt@PEG consists of a NIR fluorophore for tracing drug release, a nonspecific antitumor drug cisplatin for hepatocellular carcinoma treatment, a glutathione‐activatable disulfide linker, and a DSPE‐mPEG nano‐micelle carrier for controllable drug release. DCM‐S‐Pt@PEG can make the drug accumulation in tumor tissues enhance the therapeutic effect by: i) specific delivery of prodrug to hepatic tumor tissues through the femoral artery by TIT, ii) sustained drug‐release from the biodegradable lipid DSPE‐mPEG micelle to minimize metabolic clearance, and iii) cancer biomarker–activated drug release. It provides a promising strategy to assist TIT in treating unresectable devastating hepatocellular carcinoma administration in the rabbit model, rather than common mouse model.