Emerging evidence has demonstrated that stromal cell-derived factor 1(SDF-1)and its cognate receptor CXCR4 have critical roles in tumorigenesis,angiogenesis and metastasis.In this study,we demonstrated the significant inhibitory effects of a novel chemically synthetic peptide(E5)on the CXCR4/CXCL12 axis in breast cancer both in vitro and in vivo.E5 was capable of specifically binding to the murine breast cancer cell line 4T1,remarkably inhibiting CXCL12-or stromal cell(MS-5)-induced migration,and adhesion and sensitizing 4T1 cells to multiple chemotherapeutic drugs.Furthermore,E5 combined with either paclitaxel or cyclophosphamide significantly inhibited tumor growth in a breast cancer model.Mechanistic studies implied that E5 can inhibit the expression of CXCR4 to block the CXCL12-mediated recruitment of endothelial progenitor cells and repress CXCR4 downstream of the Akt and Erk signaling pathway,which are involved in tumor angiogenesis and progression.Further pharmacokinetic evaluation suggested that E5 has an acceptable stability,with a half-life of 10 h in healthy mice.In conclusion,E5 demonstrates a promising anti-tumor effect and could be a potential chemotherapeutic sensitizer to improve current clinical breast cancer therapies.
The formation of coordinated dimeric complexes bridged by axial ligands on surface is observed with the help of a 1,3,5-tris(10-carboxydecyloxy)benzene(TCDB) template through scanning tunneling microscopy(STM). STM images of molecular adlayers of zinc tetraphenylporphyrin(Zn TPP), zinc phthalocyanine(Zn Pc), and their mixture are reported. Zn TPP and Zn Pc can spontaneously form highly an ordered structure with a 1:1 molar ratio, which is different from that of individual Zn Pc. The coordinated bimolecular complexes bridged with axial ligands, simply as Zn Pc–DPP–Zn TPP and Zn Pc–DPE–Zn Pc, are presented and the corresponding surface structures are compared. Zn Pc and Zn TPP can be connected by an axial ligand DPP and formed assembled structures out of surface. Two types of arrays with entirely new structure are obtained for the Zn Pc–DPE–Zn Pc complex. These bridged hybrid complexes provide an example of design of self-organized crystals on the basis of coordination through non-covalent interactions.
Yan-Fang GengShi-Li WuJing XuHong-Liang DaiXiao-Kang LiKe DengQing-Dao Zeng
Accumulation and aggregation of β-amyloid(Aβ) peptides result in neuronal death, leading to cognitive dysfunction in Alzheimer's disease. The self-assembled Aβ molecules form various intermediate aggregates including oligomers that are more toxic to neurons than the mature aggregates, including fibrils. Thus, one strategy to alleviate Aβ toxicity is to facilitate the conversion of Aβ intermediates to larger aggregates such as fibrils. In this study, we designed a peptide named A3 that significantly enhanced the formation of amorphous aggregates of Aβ by accelerating the aggregation kinetics. Thioflavin T fluorescence experiments revealed an accelerated aggregation of Aβ monomers, accompanying reduced Aβ cytotoxicity. Transgenic Caenorhabditis elegans over-expressing amyloid precursor protein exhibited paralysis due to the accumulation of Aβ oligomers, and this phenotype was attenuated by feeding the animals with A3 peptide. These findings suggest that the Aβ aggregation-promotion effect can potentially be useful for developing strategies to reduce Aβ toxicity.
Aihua YangChenxuan WangBaomin SongWendi ZhangYuanyuan GuoRong YangGuangjun NieYanlian YangChen Wang
Supramolecular self-assembly,an important strategy in nanotechnology,has been widely studied in the past two decades.In this review,we have introduced the recent progress on construction of two-dimensional(2D)nanostructures by host-guest supramolecular chemistry at solid-liquid interface,and the interactions between the host assembly and the guest molecules are the major concerns.At first,the hydrogen bonds connected hybrid structures are discussed.And then we have paid a close attention on the surface-confined condensation reactions that has flourished recently in direct preparing novel nanostructures with increasing structural complexity.In the end,the cavity confinement of the 2D supramolecular host-guest architectures has been studied.On the basis of the above-mentioned interactions,a group of functional hybrid structures have been prepared.Notably,scanning tunneling microscopy(STM),a unique technique to probe the surface morphology and information at the single molecule level,has been used to probe the formed structures on highly oriented pyrolytic graphite(HOPG)surface.
