Tuesday, April 22, 2014

Colorectal cancer treatment via mPEG-PLA micelles

PolySciTech (www.polyscitech.com) provides a wide array of mPEG-PLA as well as active endcap PEG-PLA block copolymers with –COOH, -NHS, -Maleimide and other active endcaps. Recently these types of polymers were applied to treatment of colorectal cancer cells in-vivo using the F56 targeting peptide and delivering vincristine. Read more: Wang, Chao, Mei Zhao, Ya-Rong Liu, Xin Luan, Ying-Yun Guan, Qin Lu, De-Hong Yu, Fan Bai, Hong-Zhuan Chen, and Chao Fang. "Suppression of colorectal cancer subcutaneous xenograft and experimental lung metastasis using nanoparticle-mediated drug delivery to tumor neovasculature." Biomaterials 35, no. 4 (2014): 1215-1226. http://dx.doi.org/10.1016/j.biomaterials.2013.08.091


“Abstract: Antiangiogenic therapy is a validated approach for colorectal cancer (CRC) treatment. However, diverse adverse effects inevitably appear due to the off-target effect of the approved antiangiogenic inhibitors on the physiological functions and homeostasis. This study was to investigate a new tumor vessel targeting nanoparticulate drug delivery system, F56 peptide conjugated nanoparticles loading vincristine (F56-VCR-NP), for the effective treatment of CRC subcutaneous xenograft and experimental lung metastasis model. The controlled release behavior and in vivo pharmacokinetic profile of F56-VCR-NP were characterized. The tumor vessel targeting and antiangiogenic activity of F56-VCR-NP was evaluated in human umbilical vein endothelial cells (HUVEC, a classical cell model mimicking tumor vascular EC), subcutaneous human HCT-15 xenograft in immunodeficient nude mice, and experimental CT-26 lung metastasis model in immunocompetent mice. The therapeutic efficacy (animal survival and toxicity) was further investigated in the model of CT-26 lung metastasis in mice. F56-VCR-NP could achieve 30-day controlled drug release in PBS (pH 7.4) and exhibited favorable long-circulating feature in vivo. F56-VCR-NP could accurately target the CRC neovasculature and elicit nanoparticle internalization in the tumor vascular EC, where the antiangiogenic VCR-induced dramatic EC apoptosis and necrosis of CRC tissue. F56-VCR-NP significantly prolonged the mouse survival with no obvious toxicity (weight loss and anepithymia) in the CT-26 lung metastasis mice model, and this pronounced antitumor effect was closely related with the decreased microvessel density in the metastases. The present nanoparticle-based targeted antiangiogenic therapy may provide a new promising approach for the therapy of CRC and lung metastasis, which deserves further translational research. Keywords: Tumor neovasculature; Nanoparticles; Antiangiogenic therapy; Colorectal cancer; Lung metastasis”
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