Thursday, July 9, 2015

PolyVivo PLGA-PEG-COOH used for nanoparticle based liver cancer therapy

PolySciTech (www.polyscitech.com) provides a wide array of polymer products including PolyVivo AI034 (PLGA-PEG-COOH). Recently this polymer was used to develop targeted nanoparticles that deliver salinomycin to cancer cells. Salinomycin typically acts as an antibiotic, but it has recently been discovered to also have cancer therapeutic effects in that it kills cancer stem cells even when the cancer is resistant to other therapies. High doses of salinomycin, however, can have toxic side effects necessitating a targeted delivery scheme so that a smaller, targeted dose can be administered (see http://www.hindawi.com/journals/bmri/2012/950658/ for an excellent review of salinomycin).  Nanoparticles cannot be controlled in the way that they move through the blood-stream but they can be chemically attached to specific proteins which preferentially adhere to cancer cell markers (named ‘aptamers’ or ‘ligands’). In this way, these nanoparticles can have their motion controlled by making them ‘stick’ to cancer cells. Recently, Jiang and coworkers utilized PLGA-PEG-COOH for conjugating cancer specific aptamers A15 and CL4, which target to the cancer markers CD133 and EGFR respectively, so as to generate a nanoparticle which preferentially adhere to liver cancer cells. These particles were then loaded with salinomycin and tested in a mouse tumor model. These were found to have good efficacy against liver cancer (hepatocellular carcinoma). Read more:  Jiang, Jianxin, Huaiwen Chen, Chao Yu, Yingying Zhang, Meiyuan Chen, She Tian, and Chengyi Sun. "The promotion of salinomycin delivery to hepatocellular carcinoma cells through EGFR and CD133 aptamers conjugation by PLGA nanoparticles." Nanomedicine 10, no. 12 (2015): 1863-1879. http://www.futuremedicine.com/doi/abs/10.2217/nnm.15.43


“Abstract: Aims: To develop salinomycin-loaded poly(lactic-co-glycolic acid) nanoparticles conjugated with both CD133 aptamers A15 and EGFR aptamers CL4 (CESN), to target hepatocellular carcinoma (HCC) cells simultaneously expressing EGFR and CD133. Materials & methods: The antitumor activity and mechanism of CESN were investigated. Results & conclusion: The cytotoxicity of CESN in HCC cells and CD133+ HCC cells was superior to that of A15 or CL4-conjugted or nontargeted salinomycin-loaded nanoparticles. The antitumor assay in mice bearing HCC xenograft tumors confirmed the superior antitumor activity of CESN over other controls. We speculated that the improved therapeutic effect of CESN may be attributed to both targeting a higher percentage of HCC cells and increased delivery of salinomycin to HCC cells.”
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