LiveG4ID-Seq for Profiling the Dynamic Landscape of Chromatin G-Quadruplexes During Cell Cycle in Living Cells.

G-quadruplex (G4) structures exist in the single-stranded DNA of chromatin and regulate genome function. However, the native chromatin G4 landscape in living cells has yet to be fully characterized. Herein, a genetic-encoded live-cell G4 identifier probe (LiveG4ID) is constructed and its cellular localization, biocompatibility, and G4-binding specificity is evaluated. By coupling LiveG4ID with cleavage under targets and tagmentation (CUT&Tag), LiveG4ID-seq, a method for mapping native chromatin G4 landscape in living cells with high accuracy is established. Compared to the conventional G4 CUT&Tag method, LiveG4ID-seq can identify more chromatin G4 signals and have a higher ratio of true positive signals. Using LiveG4ID-seq, the dynamic landscape of chromatin G4 structures during the cell cycle is profiled. It is discovered that chromatin G4 structures are prevalent in the promoter regions of cell cycle-specific genes, even in the early M phase when the chromatin is condensed. These data demonstrate the capacity of LiveG4ID-seq to profile a more accurate G4 landscape in living cells and promote future studies on chromatin G4 structures.

Ovalbumin-modified nanoparticles increase the tumor accumulation by a tumor microenvironment-mediated "giant".

We designed a pH intelligently driven self-assembled nano-platform (GOx@ZIF-OVA). The nano-platform was composed of glucose oxidase (GOx), ovalbumin (OVA) and zeolitic imidazolate skeleton-8 (ZIF-8). The goal was to address the depth and cumulative limits of the drug at the tumor site. Firstly, OVA-modified GOx@ZIF could greatly increase tumor accumulation due to spontaneous self-assembly from 142.2 ± 9.1 to 705.5 ± 52.1 nm and the 5779.4 ± 598.3 nm giant at pH values of 7.4, 6.5, and 5.0, respectively. More importantly, the tumor-like sphere experiments demonstrated that the encapsulated GOx "vampires" can cut off the energy source of tumors and poisonous tumor cells without depth limitations. Furthermore, immunofluorescence assay and cytotoxicity assay tests in vivo proved that T cell infiltration could be significantly increased, triggering an effective anti-tumor immune response and inhibiting lung metastasis. Therefore, the experimental results demonstrated that the acid-smart-driven nano-platform has the potential to address the limitations of tumor depth and drug accumulation in solid tumors.