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Background: Identification of promising targeted antigens that exhibited cancer-specific expression is a crucial step in the development of novel antibody-targeted therapies. We here aimed to investigate the anti-tumor activity of a novel monoclonal antibody (mAb) 11C9 and identify the antibody tractable target in the hepatocellular cancer stem cells (HCSCs). Methods: The identification of the targeted antigen was conducted using SDS-PAGE, western blot, mass spectrometry, and co-immunoprecipitation. Silence of HSP90 was induced by siRNA interference. Positive cells were sorted by fluorescence-activated cell sorting. Double-immunofluorescent (IF) staining and two-color flow cytometry detected the co-expression. Self-renewal, invasion, and drug resistance were assessed by sphere formation, matrigel-coated Transwell assay, and CCK-8 assay, respectively. Tumorigenicity was evaluated in mouse xenograft models. RNA-seq and bioinformatics analysis were performed to explore the mechanism of mAb 11C9 and potential targets. Results: MAb 11C9 inhibited invasion and self-renewal abilities of HCC cell lines and reversed the cisplatin resistance. HSP90 (~ 95 kDa) was identified as a targeted antigen of mAb 11C9. Tissue microarrays and online databases revealed that HSP90 was overexpressed in HCC and associated with a poor prognosis. FACS and double-IF staining showed the co-expression of HSP90 and CSCs markers (CD90 and ESA). In vitro and in vivo demonstrated the tumorigenic potentials of HSP90. The inhibition of HSP90 by siRNA interference or 17-AAG inhibitor both decreased the number of invasion, sphere cells, and CD90+ or ESA+ cells, as well as reversed the resistance. Bioinformatics analysis and western blot verified that HSP90 activated Wnt/β-catenin signaling. Conclusions: The study preliminarily revealed the anti-tumor activity of mAb 11C9. More importantly, we identified HSP90 as a targeted antigen of mAb 11C9, which functions as an oncogene in phenotype shaping, stemness maintenance, and therapeutic resistance by activating Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

• Two heteronuclear 3d-4f complexes (Ln = Tb, Gd) were synthesized using the compartmental Schiff base ligand and secondary sulfonate co-ligands. • These compounds represent rare instances of dinuclear Co(III)-Ln(III) SMMs. • These findings demonstrate the practicality of creating sulfonate-based Co(III)-Ln(III) coordination complexes, despite sulfonate's generally weak bonding with metal ions. • This research not only broaden the structural diversity of 3d-4f complexes but also provide a valuable experimental basis for further exploration of their magnetic properties. In this research, our team synthesized and characterized two heteronuclear 3d-4f complexes, [CoIIICl(μ -valen)(μ -4-HBS)LnIII(NO 3)(H 2 O)(4-HBS)], with Ln representing Tb (1) and Gd (2). Achievement of this was through the utilization of a compartmental Schiff base ligand H 2 valen, alongside secondary co-ligands Na(4-HBS) [H 2 valen=6,6′-((1E,1′E)-(ethane-1,2-diylbis(azaneylylidene))bis(methaneylylidene))bis(2-methoxyphenol); Na(4-HBS)=sodium 4-hydroxybenzenesulfonate]. X-ray crystallography revealed that both complexes feature a similar [Co(III)-Ln(III)] core, connected by the phenoxo-O atoms from the compartmental Schiff base ligand and the sulfonate-O atoms from the co-ligand. In this context, Co(III) displays a distorted octahedral geometry within a CoN 2 O 3 Cl coordination sphere, while Ln(III) exhibits a muffin (MFF)-like distorted geometry in a LnO 9 coordination sphere. Magnetic analysis shows that the two complexes display unique magnetic properties. Complex 1 exhibits pronounced SMM behavior, with a notable energy barrier of 14.8 K for magnetization reversal. However, complex 2 presents a minor energy barrier of 4.8 K. Additionally, complexes 1 and 2 represent uncommon examples of dinuclear Co(III)-Ln(III) SMMs. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Tumor-associated antigens (TAAs) can be targeted in cancer therapy. We previously identified a monoclonal antibody (mAb) 12C7, which presented anti-tumor activity in lung cancer stem cells (LCSCs). Here, we aimed to identify the target antigen for 12C7 and confirm its role in LCSCs. Methods: Immunofluorescence was used for antigen localization. After targeted antigen purification by electrophoresis and immunoblot, the antigen was identified by LC-MALDI-TOF/TOF mass spectrometry, immunofluorescence, and immunoprecipitation. The overexpression or silence of ENO1 was induced by lentiviral transduction. Self-renewal, growth, and invasion of LCSCs were evaluated by sphere formation, colony formation, and invasion assay, respectively. High-throughput transcriptome sequencing (RNA-seq) and bioinformatics analysis were performed to analyze downstream targets and pathways of targeted antigen. Results: Targeted antigen showed a surface antigen expression pattern, and the 43–55 kDa protein band was identified as α-enolase (ENO1). Self-renewal, growth, and invasion abilities of LCSCs were remarkably inhibited by ENO1 downregulation, while enhanced by ENO1 upregulation. RNA-seq and bioinformatics analysis eventually screened 4 self-renewal-related and 6 invasion-related differentially expressed genes. GSEA analysis and qRT-PCR verified that ENO1 regulated self-renewal, invasion-related genes, and pathways. KEGG pathway analysis and immunoblot demonstrated that ENO1 inactivated AMPK pathway and activated mTOR pathway in LCSCs. Conclusions: ENO1 is identified as a targeted antigen of mAb 12C7 and plays a pivotal role in facilitating self-renewal, growth, and invasion of LCSCs. These findings provide a potent therapeutic target for the stem cell therapy for lung cancer and have potential to improve the anti-tumor activity of 12C7. [ABSTRACT FROM AUTHOR]

• Three heterometallic Ni(II)-Ln(III) complexes (Ln = Ce, Pr, Sm) were synthesized via one pot reaction using the compartmental Schiff base ligand and dicyanamide (dca). • These compounds represent rare examples of 3d-4f magnetic materials derived from dca, with few reported instances. • These findings confirm the feasibility of synthesizing dca-bridged Ni(II)-Ln(III) complexes, despite the typically weak interaction between dca and lanthanide components. • This research not only broaden the structural diversity of 3d-4f complexes with dca bridging ligands but also provide a valuable experimental basis for further exploration of their magnetic properties. Three heterometallic Ni(II)-Ln(III) complexes (Ln = Ce, Pr, Sm), with the formulas [(Ni(μ -L)Ce(NO 3)(dca)(μ -dca)] n (1), [Ni(μ -L)Pr(NO 3) 2 (CH 3 OH)(dca)] (2) and [Ni(μ -L)Sm(NO 3)(NO 3 Cl)(μ -dca)] (3) were synthesized via one pot reaction using the compartmental ligand H 2 L and dicyanamide [H 2 L=6,6′-((1E,1′E)-(ethane-1,2-diylbis(azaneylylidene))bis(methaneylylidene))bis(2-methoxyphenol); dca= dicyanamide]. For complexes 1 – 3 , all Ni atoms exhibit tetra-coordination with square (D 4h) geometry, while all Ln (Ce, Pr and Sm) atoms display deca-coordination with sphenocorona (C 2v) geometry. Complex 1 displays a one-dimensional (1D) infinite chain structure, where [NiIICeIII] dinuclear units form tetranuclear [NiIICeIII] 2 clusters, bridged by dca ligands. Similarly, complex 3 exhibits a 1D chain structure, with [NiIISmIII] dinuclear units directly bridged by dca ligands. In contrast, complex 2 exists as isolated monomers, with dca acting as a terminal ligand. Additionally, the magnetic properties of these complexes were investigated and analyzed. These compounds represent rare examples of 3d-4f magnetic materials derived from dca, with few reported instances. [ABSTRACT FROM AUTHOR]