Monday, July 28, 2014

PEG-PLA and cationic derivatives used as part of SiRNA therapy for triple negative breast cancer

PolySciTech ( provides a variety of PEG-PLA block copolymers as well as cationic polymers such as cationic CPLA derivatives and PEI derivatives. Recently combinations of PEG-PLA block copolymers and cationic derivatives have been utilized for delivery of SiRNA inducing apoptosis in cancer cells. Read more: Liu, Yang, Yan-Hua Zhu, Cheng-Qiong Mao, Shuang Dou, Song Shen, Zi-Bin Tan, and Jun Wang. "Triple Negative Breast Cancer Therapy with CDK1 siRNA Delivered by Cationic Lipid Assisted PEG-PLA Nanoparticles." Journal of Controlled Release (2014).

“Abstract: There is no effective clinical therapy yet for triple-negative breast cancer (TNBC) without particular human epidermal growth factor receptor-2, estrogen and progesterone receptor expression. In this study, we report a molecularly targeted and synthetic lethality-based siRNA therapy for TNBC treatment, using cationic lipid assisted poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PLA) nanoparticles as the siRNA carrier. It is demonstrated that only in c-Myc overexpressed TNBC cells, while not in normal mammary epithelial cells, delivery of siRNA targeting cyclin-dependent kinase 1 (CDK1) with the nanoparticle carrier (NPsiCDK1) induces cell viability decreasing and cell apoptosis through RNAi-mediated CDK1 expression inhibition, indicating the synthetic lethality between c-Myc with CDK1 in TNBC cells. Moreover, systemic delivery of NPsiCDK1 is able to suppress tumor growth in mice bearing SUM149 and BT549 xenograft and cause no systemic toxicity or activate the innate immune response, suggesting the therapeutic promise with such nanoparticles carrying siCDK1 for c-Myc overexpressed triple negative breast cancer. Keywords: Triple-negative breast cancer; Synthetic lethality; siRNA delivery; Cationic lipid assisted nanoparticle; Cyclin-dependent kinase 1”

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