Clay-based nanomaterials, especially 2:1 aluminosilicates such as vermiculite, biotite, and illite, have demonstrated great potential in various fields. However, their characteristic sandwiched structures and the lack of effective methods to exfoliate two-dimensional (2D) functional core layers (FCLs) greatly limit their future applications. Herein, we present a universal wet-chemical exfoliation method based on alkali etching that can intelligently “capture” the ultrathin and biocompatible FCLs (MgO and Fe₂O₃) sandwiched between two identical tetrahedral layers (SiO₂ and Al₂O₃) from vermiculite. Without the sandwich structures that shielded their active sites, the obtained FCL nanosheets (NSs) exhibit a tunable and appropriate electron band structure (with the bandgap decreased from 2.0 eV to 1.4 eV), a conductive band that increased from −0.4 eV to −0.6 eV, and excellent light response characteristics. The great properties of 2D FCL NSs endow them with exciting potential in diverse applications including energy, photocatalysis, and biomedical engineering. This study specifically highlights their application in cancer theranostics as an example, potentially serving as a prelude to future extensive studies of 2D FCL NSs.

Biotite, also called black mica (BM), is a group of sheet silicate minerals with great potential in various fields. However, synthesis of high‐quality BM nanosheets (NSs) remains a huge challenge. Here, an exfoliation approach is provided that combines calcination, n‐butyllithium exchange and intercalation, and liquid exfoliating processes for the high‐yield synthesis of ultrathin BM NSs. Due to the presence of MgO, Fe₂O₃, and FeO in these NSs, PEGylated BM can be engineered as an intelligent theranostic platform with the following unique features: i) Fe³⁺ can damage the tumor microenvironment (TME) through glutathione consumption and O₂ production; ii) Generated O₂ can be further catalyzed by MgO with oxygen vacancy to generate ·O₂⁻; iii) The Fe²⁺‐catalyzed Fenton reaction can produce ·OH by disproportionation reactions of H₂O₂ in the TME; iv) Reactions in (i) and (iii) circularly regenerate Fe²⁺ and Fe³⁺ for continuous consumption of glutathione and H₂O₂ and constant production of ·OH and O₂; v) The NSs can be triggered by a 650 nm laser to generate ·O₂⁻ from O₂ as well as by an 808 nm laser to generate local hyperthermia; and vi) The fluorescent, photoacoustic, and photothermal imaging capabilities of the engineered NSs allow for multimodal imaging‐guided breast cancer treatment.

Isoginkgetin (ISO), a natural biflavonoid, exhibited cytotoxic activity against several types of cancer cells. However, its effects on hepatocellular carcinoma (HCC) cells and mechanism remain unclear. Here, we revealed that ISO effectively inhibited HCC cell proliferation and migration in vitro. LC3-II expression and autophagosomes were increased under ISO treatment. In addition, ISO-induced cell death was attenuated by treatment with chloroquine or knockdown of autophagy-related genes (ATG5 or ULK1). ISO significantly suppressed SLC2A1/GLUT1 (solute carrier family 2 member 1) expression and glucose uptake, leading to activation of the AMPK-ULK1 axis in HepG2 cells. Overexpression of SLC2A1/GLUT1 abrogated ISO-induced autophagy. Combining molecular docking with thermal shift analysis, we confirmed that ISO directly bound to the N terminus of CDK6 (cyclin-dependent kinase 6) and promoted its degradation. Overexpression of CDK6 abrogated ISO-induced inhibition of SLC2A1/GLUT1 transcription and induction of autophagy. Furthermore, ISO treatment significantly decreased the H3K27ac, H4K8ac and H3K4me1 levels on the SLC2A1/GLUT1 enhancer in HepG2 cells. Finally, ISO suppressed the hepatocarcinogenesis in the HepG2 xenograft mice and the diethylnitrosamine+carbon tetrachloride (DEN+CCl₄)-induced primary HCC mice and we confirmed SLC2A1/GLUT1 and CDK6 as promising oncogenes in HCC by analysis of TCGA data and human HCC tissues. Our results provide a new molecular mechanism by which ISO treatment or CDK6 deletion promotes autophagy; that is, ISO targeting the N terminus of CDK6 for degradation inhibits the expression of SLC2A1/GLUT1 by decreasing the enhancer activity of SLC2A1/GLUT1, resulting in decreased glucose levels and inducing the AMPK-ULK1 pathway.

Lonicera japonica Thunb., possesses antiviral and hepatoprotective activities, and is widely used as a health food and in cosmetics. However, its major constituents, caffeoylquinic acid derivatives, and their anti-HBV activity were lacking systematic research. In this study, four novel caffeoylquinic acids, five simple caffeic acids and fourteen known caffeoylquinic acids are isolated and identified from L. japonica. Most caffeoylquinic acids inhibited HBsAg and HBeAg secretion, and HBV DNA replication. In particular, 100 μg ml⁻¹ monocaffeoylquinic acid 9 inhibits HBsAg and HBeAg secretion, and HBV DNA replication by 83.82, 70.76 and 39.36% compared to the control. Unfortunately, 50 μg ml⁻¹ tricaffeoylquinic acid 23 promotes HBsAg and HBeAg secretion, and HBV DNA replication by 172.39, 9.92 and 55.40%. Finally, structure–activity relationships reveal that caffeoylquinic acids containing a caffeoyl group have better inhibitory activities. The results indicate that caffeoylquinic acids from L. japonica could serve as anti-HBV agents for functional food or medicinal use.