Thermally Stable Metallic Nanoparticles Prepared via Core-Cross-linked Block Copolymer Micellar Nanoreactors

Thermally stable metallic nanoparticles (MNPs) are highly desirable for the melt processing of polymer nanocomposites. However, due to the high surface energy penalty and decreased melting temperature, MNPs are easy to agglomerate and lose their unique properties if there is no protection or confinement layer. In this work, we report a facile and efficient way to synthesize thermally stable MNPs using core-cross-linked polystyrene-<i>b</i>-poly­(4-vinylpyridine) (PS-<i>b</i>-P4VP) reverse micelles as nanoreactors. From infrared results, gold, silver, and palladium ions exhibited distinctive coordination to the 4VP groups with varying chelation strengths. Compared to the non-cross-linked micelles, 1,4-dibromobutane (DBB)-cross-linking of the P4VP cores provided several advantages. First, it prevented severe swelling of the P4VP cores caused by the reducing agents and subsequent merger of swollen micelles. Second, the quaternized P4VP with hydrophilicity enhanced the uptake speed of precursor metal ions into the cores. Third, the cross-linked cores greatly stabilized the MNPs against the high-temperature environment (<i>e.g.</i>, 110 °C for 40 h in toluene). In addition, the solubility of the reducing agents also played an important role. Anhydrous hydrazine could swell the P4VP cores and concentric core–shell particle morphology was obtained. On the contrary, triethylsilane could not swell the P4VP cores and thus eccentric core–shell particle morphology was observed. Only the concentric core–shell MNPs exhibited good thermal stability, whereas the eccentric core–shell MNPs did not. This work suggested that these thermally stable MNPs could be good candidates for the melt processing of functional polymer nanocomposites

A prognostic model of drug tolerant persister-related genes in lung adenocarcinoma based on single cell and bulk RNA sequencing data

Background: Acquired resistance to targeted drugs is a major challenge in cancer. The drug-tolerant state has been proposed to be an initial step towards acquisition of real drug-resistance. Drug tolerant persister (DTP) cells are purported to survive during treatment and stay dormant for several years. Single cell sequencing can provide a comprehensive landscape of gene expression in DTP cells, which can facilitate investigation of heterogeneity of a drug tolerant state and identification of new anticancer targets. Methods: The genetic profiling of DTPs was explored by integrating Gene Expression Omnibus (GEO) datasets, and a prognostic signature of DTP-related genes (DTPRGs) in lung adenocarcinoma of TCGA LUAD cohort was constructed. The scores of infiltrating immune cells were calculated and activity of immune-related pathways was evaluated by single-sample gene set enrichment analysis (ssGSEA). Functional enrichment analysis of the DTPRGs between low- and high-risk groups was performed. Immune cell subtypes and immune-related pathways were analyzed. Results: An 11-gene panel (MT2A, UBE2S, CLTB, KRT7, IGFBP3, CTSH, NPC2, HMGA1, HNRNPAB, DTYMK, and IHNA) was established. DTPRGs were mainly correlated with nuclear division, chromosome segregation, and cell cycle pathways. Infiltration of immune cells was lower in the high-risk group while the inflammation-promoting and MCH-class I response pathway had higher activity in the high-risk group. A nomogram was generated with prognostic accuracy, further validated using clinical outcomes following therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Discussion: A prognostic model of lung adenocarcinoma based on DTPRGs was constructed. Targeting DTP cells is a potential therapeutic approach to prevent a drug tolerant state