Functional 2D Nanoplatforms Alleviate Eosinophilic Chronic Rhinosinusitis by Modulating Eosinophil Extracellular Trap Formation.

The therapeutic outcomes of patients with eosinophilic chronic rhinosinusitis (ECRS) remain unsatisfactory, largely because the underlying mechanisms of eosinophilic inflammation are uncertain. Here, it is shown that the nasal secretions of ECRS patients have high eosinophil extracellular trap (EET) and cell-free DNA (cfDNA) levels. Moreover, the cfDNA induced EET formation by activating toll-like receptor 9 (TLR9) signaling. After demonstrating that DNase I reduced eosinophilic inflammation by modulating EET formation, linear polyglycerol-amine (LPGA)-coated TiS2 nanosheets (TLPGA) as functional 2D nanoplatforms with low cytotoxicity, mild protein adsorption, and increased degradation rate is developed. Due to the more flexible linear architecture, TLPGA exhibited higher cfDNA affinity than the TiS2 nanosheets coated with dendritic polyglycerol-amine (TDPGA). TLPGA reduced cfDNA levels in the nasal secretions of ECRS patients while suppressing cfDNA-induced TLR9 activation and EET formation in vitro. TLPGA displayed exceptional biocompatibility, preferential nasal localization, and potent inflammation modulation in mice with eosinophilic inflammation. These results highlight the pivotal feature of the linear molecular architecture and 2D sheet-like nanostructure in the development of anti-inflammation nanoplatforms, which can be exploited for ECRS treatment.

Construction of CpG Delivery Nanoplatforms by Functionalized MoS2 Nanosheets for Boosting Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.

Despite the promising achievements of immune checkpoint blockade (ICB) therapy for tumor treatment, its therapeutic effect against solid tumors is limited due to the suppressed tumor immune microenvironment (TIME). Herein, a series of polyethyleneimine (Mw = 0.8k, PEI0.8k )-covered MoS2 nanosheets with different sizes and charge densities are synthesized, and the CpG, a toll-like receptor-9 agonist, is enveloped to construct nanoplatforms for the treatment of head and neck squamous cell carcinoma (HNSCC). It is proved that functionalized nanosheets with medium size display similar CpG loading capacity regardless of low or high PEI0.8k coverage owing to the flexibility and crimpability of 2D backbone. CpG-loaded nanosheets with medium size and low charge density (CpG@MM -PL ) could promote the maturation, antigen-presenting capacity, and proinflammatory cytokines generation of bone marrow-derived dendritic cells (DCs). Further analysis reveals that CpG@MM -PL effectively boosts the TIME of HNSCC in vivo including DC maturation and cytotoxic T lymphocyte infiltration. Most importantly, the combination of CpG@MM -PL and ICB agents anti-programmed death 1 hugely improves the tumor therapeutic effect, inspiring more attempts for cancer immunotherapy. In addition, this work uncovers a pivotal feature of the 2D sheet-like materials in nanomedicine development, which should be considered for the design of future nanosheet-based therapeutic nanoplatforms.

U1RNP/lncRNA/Transcription Cycle Axis Promotes Tumorigenesis of Hepatocellular Carcinoma.

As a component of the spliceosome, U1 small nuclear ribonucleoproteins (U1RNPs) play critical roles in RNA splicing, and recent studies have shown that U1RNPs could recruit long non-coding RNAs (lncRNAs) to chromatin which are involved in cancer development. However, the interplay of U1 snRNP, lncRNAs and downstream genes and signaling pathways are insufficiently understood in hepatocellular carcinoma (HCC). The expression of U1RNPs was found to be significantly higher in tumors than normal tissues in liver hepatocellular carcinomas of The Cancer Genome Atlas (TCGA-LIHC) dataset. LncRNAs with potential U1-binding sites (termed U1-lncRNAs) were found to be mostly located in the nucleus and their expression was higher in tumor than in normal tissues Bioinformatic analysis indicated that U1-lncRNAs worked with RNA-binding proteins and regulated the transcription cycle in HCC. A U1-lncRNA risk model was constructed using a TCGA dataset, and the AUCs of this risk model to predict 1-, 3- and 5-year overall survival were 0.82, 0.84 and 0.8, respectively. Furthermore, silencing of the small nuclear ribonucleoprotein D2 polypeptide (SNRPD2) resulted in impaired proliferation, G1/M cell cycle arrest and downregulation of transcription-cycle-related genes in HCC cell lines. Taken together, these results indicate that U1RNPs interact with lncRNAs and promote the transcription cycle process in HCC, which suggests that these could be novel biomarkers in the clinical management of HCC.