Discovery of a near-infrared fluorescent probe for G-quadruplexes by exploiting the concept of unfolding-intramolecular-aggregation-induced emission.

In the very recent years, the concept of disaggregation-induced emission (DIE) has been applied to design G4 probes, thereby rendering several fluorophores that may suffer from aggregation-induced quenching (ACQ) to develop into desirable G4-selective probes. However, the design idea based on DIE was often limited by the instability and irreversibility of the "intermolecular" aggregation/disaggregation process. In this study, a self-folded, near-infrared fluorescent probe for selectively illuminating G4s was engineered. This probe restored its fluorescence via unfolding of its intramolecular aggregation (UIA) mediated by distinctive G4 binding, which may display more controllable background emission as well as more promising ability to track G4 forming dynamics as compared to the reported DIE probes. Altogether, this study provided insights into the development of new types of applicable G4 selective fluorescent probes.

Combination Therapy with a TLR7 Agonist and a BRD4 Inhibitor Suppresses Tumor Growth via Enhanced Immunomodulation.

JQ-1 is a typical BRD4 inhibitor with the ability to directly fight tumor cells and evoke antitumor immunity via reducing the expression of PD-L1. However, problems arise with the development of JQ-1 in clinical trials, such as marked lymphoid and hematopoietic toxicity, leading to the investigation of combination therapy. SZU-101 is a TLR7 agonist designed and synthesized by our group with potent immunostimulatory activity. Therefore, we hypothesized that combination therapy of SZU-101 and JQ-1 would target innate immunity and adaptive immunity simultaneously, to achieve a better antitumor efficacy than monotherapy. In this study, the repressive effects of the combination administration on tumor growth and metastasis were demonstrated in both murine breast cancer and melanoma models. In 4T1 tumor-bearing mice, i.t. treatment with SZU-101 in combination with i.p. treatment with JQ-1 suppressed the growth of tumors at both injected and uninjected sites. Combination therapy increased M1/M2 ratio in TAMs, decreased PD-L1 expression and promoted the recruitment of activated CD8+ T cells in the TME. In summary, the improved therapeutic efficacy of the novel combination therapy appears to be feasible for the treatment of a diversity of cancers.

Discovery of a triphenylamine-based ligand that targets mitochondrial DNA G-quadruplexes and activates the cGAS-STING immunomodulatory pathway.

Stabilization of G-quadruplex (G4) structures in mitochondria leads to the damage of mitochondrial DNA (mtDNA), making mtDNA G4s a promising target in the field of cancer therapy in recent years. Damaged mtDNA released into the cytosol can stimulate cytosolic DNA-sensing pathways, and cGAS-STING pathway is a typical one with potent immunostimulatory effects. A few small molecule ligands of mtDNA G4s are identified with antitumor efficacy, but little is known about their results and mechanisms on immunomodulation. In this study, we engineered a series of triphenylamine-based analogues targeting mtDNA G4s, and A6 was determined as the most promising compound. Cellular studies indicated that A6 caused severe mtDNA damage. Then, damaged mtDNA stimulated cGAS-STING pathway, resulting in the following cytokine production of tumor cells and the maturation of DCs. In vivo experiments certified that A6 exerted suppressive influences on tumor growth and metastasis in 4T1 cell-bearing mice by the regulation of TME, including the remodeling of macrophages and the activation of T cells. To our knowledge, it is the first time to report a ligand targeting mtDNA G4s to activate the cGAS-STING immunomodulatory pathway, providing a novel strategy for the future development of mtDNA G4-based antitumor agents.

Cyano-Coordinated Tin Halide Perovskites for Wearable Health Monitoring and Weak Light Imaging.

Low-toxicity tin halide perovskites with excellent optoelectronic properties are promising candidates for photodetection. However, tin halide perovskite photodetectors have suffered from high dark current owing to uncontrollable Sn2+ oxidation. Here, 2-cyanoethan-1-aminium iodide (CNI) is introduced in CH(NH2)2SnI3 (FASnI3) perovskite films to inhibit Sn2+ oxidation by the strong coordination interaction between the cyano group (C≡N) and Sn2+. Consequently, FASnI3-CNI films exhibit reduced nonradiative recombination and lower trap density. The self-powered photodetector based on FASnI3-CNI exhibits low dark current (1.04 × 10-9 A cm-2), high detectivity (2.2 × 1013 Jones at 785 nm), fast response speed (2.62 µs), and good stability. Mechanism studies show the increase in the activation energy required for thermal emission and generated carriers, leading to a lower dark current in the FASnI3-CNI photodetector. In addition, flexible photodetectors based on FASnI3-CNI, exhibiting high detectivity and fast response speed, are employed in wearable electronics to monitor the human heart rate under weak light and zero bias conditions. Finally, the FASnI3-CNI perovskite photodetectors are integrated with a 32 × 32 thin-film transistor backplane, capable of ultraweak light (170 nW cm-2) real-time imaging with high contrast, and zero power consumption, demonstrating the great potential for image sensor applications.

Two-Dimensional SnSe2(1-x)S2x/MoTe2 Antiambipolar Transistors with Composition Modulation for Multivalued Inverters.

Two-dimensional (2D) van der Waals heterostructures that embody the electronic characteristics of each constituent material have found extensive applications. Alloy engineering further enables the modulation of the electronic properties in these structures. Consequently, we envisage the construction and modulation of composition-dependent antiambipolar transistors (AATs) using van der Waals heterostructures and alloy engineering to advance multivalued inverters. In this work, we calculate the electron structures of SnSe2(1-x)S2x alloys and determine the energy band alignment between SnSe2(1-x)S2x and 2H-MoTe2. We present a series of vertical AATs based on the SnSe2(1-x)S2x/MoTe2 type-III van der Waals heterostructure. These transistors exhibit composition-dependent antiambipolar characteristics through the van der Waals heterostructure, except for the SnSe2/MoTe2 transistor. The peak current (Ipeak) decreases from 43 nA (x = 0.25) to 0.8 nA (x = 1) at Vds = -2 V, while the peak-to-valley current ratio (PVR) increases from 4.5 (x = 0.25) to 6.7 × 103 (x = 1) with a work window ranging from 30 to 47 V. Ultimately, we successfully apply several specific SnSe2(1-x)S2x/MoTe2 devices in binary and ternary logic inverters. Our results underscore the efficacy of alloy engineering in modulating the characteristics of AATs, offering a promising strategy for the development of multivalued logic devices.