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Chemokine receptor CXCR4 plays an important role in cancer cell invasion and metastasis. Recent findings suggest that anti-VEGF therapies upregulate CXCR4 expression, which contributes to resistance to antiangiogenic therapies. Here, we report the development of novel derivatives of polyethylenimine (PEI) that effectively inhibit CXCR4 while delivering anti-VEGF siRNA. PEI was alkylated with different amounts of a CXCR4-binding cyclam derivative to prepare PEI-C. Modification with the cyclam derivatives resulted in a considerable decrease in cytotoxicity when compared with unmodified PEI. All the PEI-C showed significant CXCR4 antagonism and the ability to inhibit cancer cell invasion. Polyplexes of PEI-C prepared with siVEGF showed effective silencing of the VEGF expression in vitro. In vivo testing in a syngeneic breast cancer model showed promising antitumor and antimetastatic activity of the PEI-C/siVEGF polyplexes. Our data demonstrate the feasibility of using PEI-C as a carrier for simultaneous VEGF...
| Authors: | Yiwen Zhou; Fei Yu; Feiran Zhang; Gang Chen; Kaikai Wang; Minjie Sun; Jing Li; David Oupický | |
| Journal: | Biomacromolecules | |
| Year: | 2018 | |
| DOI: | 10.1021/acs.biomac.7b01487 | |
| Publication date: | 19-Jan-2018 |
The molecular structures of three parthenolide analogues, (−)-goyazensolide (1), (−)-15-deoxygoyazensolide (2), and (−)-ereglomerulide (3), isolated from the leaves of Piptocoma rufescens in a previous study were determined by X-ray analysis, and the absolute configuration of (−)-goyazensol ... more
Mutual Impact of Phase Separation/Crystallization and Water Sorption in Amorphous Solid Dispersions
The molecular integration of poorly water soluble active pharmaceutical ingredients (APIs) in a suitable polymeric matrix is a possible approach to enhance the dissolution behavior and solubility of these APIs. Like all newly developed pharmaceutical formulations, these formulations (often ... more
Most of the radiolabeled somatostatin analogues (SSAs) are specific for subtype somatostatin receptor 2 (SSTR2). Lack of ligands targeting other subtypes of SSTRs, especially SSTR1, SSTR3, and SSTR5, limited their applications in tumors of low SSTR2 expression, including lung tumor. In this ... more
Discovery of a biochemical basis for broccoli's cancer-fighting ability
Scientists are reporting discovery of a potential biochemical basis for the apparent cancer-fighting ability of broccoli and its veggie cousins. They found for the first time that certain substances in the vegetables appear to target and block a defective gene associated with cancer. Their ... more
Faster, more cost-effective DNA test for crime scenes, disease diagnosis
Scientists in Japan are reporting development of a faster, less expensive version of the fabled polymerase chain reaction (PCR) a DNA test widely used in criminal investigations, disease diagnosis, biological research and other applications. The new method could lead to expanded use of PCR ... more
'Nanoshells' simultaneously detect and destroy cancerous cells
Researchers at Rice University in Texas have developed a new approach to fighting cancer, based on nanoscale particles that can both detect and destroy cancerous cells. The report appears in the American Chemical Society's journal Nano Letters. Current molecular imaging approaches only dete ... more
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