Friday, June 5, 2015

PEG-PLA used as delivery system for novel cancer-metabolism inhibition system

PolySciTech (www.polyscitech.com) provides a wide array of block copolymers including poly(ethylene glycol)-b-poly(lactide) which functions as a micelle that improves water solubility of poorly soluble medicines as well as circulation times of medicines allowing them to stay in the blood-stream longer without being removed by the kidneys. In order to survive, all cells (cancerous and healthy) have to metabolize glucose for energy. Recently, PEG-PLA was used to deliver siRNA based medicines that specifically target and reduce cancer cells capability to process glucose ‘starving’ the cancer cells leading to reduced growth and proliferation.  Read more: Xu, Cong-Fei, Yang Liu, Song Shen, Yan-Hua Zhu, and Jun Wang. "Targeting glucose uptake with siRNA-based nanomedicine for cancer therapy." Biomaterials 51 (2015): 1-11. http://www.sciencedirect.com/science/article/pii/S014296121500085X


“Abstract: Targeting cancer metabolism is emerging as a successful strategy for cancer therapy. However, most of the marketed anti-metabolism drugs in cancer therapy do not distinguish normal cells from cancer cells, leading to severe side effects. In this study, we report an effective strategy for cancer therapy through targeting glucose transporter 3 (GLUT3) with siRNA-based nanomedicine to simultaneously inhibit the self-renewal of glioma stem cells and bulk glioma cells in a glucose restricted tumor micro-environment. We have demonstrated that cationic lipid-assisted poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PLA) nanoparticles can efficiently deliver siRNA into U87MG and U251 glioma stem cells and bulk glioma cells. Nanoparticles carrying specific siRNA targeting GLUT3 (NPsiGLUT3) were able to significantly reduce the expression of GLUT3 in glioma stem cells and bulk glioma cells, while GLUT3 knockdown results in obvious cell metabolism and proliferation inhibition, and further glioma stem cells percentage down-regulation. Moreover, systemic delivery of NPsiGLUT3, via intravenous injection, significantly inhibited tumor growth in a U87MG xenograft model, due to the reduced expression of GLUT3 and down-regulated stemness of glioma cells. Keywords: Nanomedicine; Cancer therapy; Glucose transporter 3; Glioma stem cells; siRNA delivery”
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