Tuesday, July 29, 2014

PEG-PLA with specific targeting for Her2+ breast cancer for SiRNA delivery

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLA block copolymers and precursors for developing nanoparticle based drug delivery technologies.  Recently PEG-PLA polymers were used to generate a nanoparticle decorated with anti-Her2 antibody fragment and shown to successfully deliver SiRNA to the cancer cells inducing apoptosis.  Read more: Dou, Shuang, Xian,Zhu Yang, Meng, Hua Xiong, Chun, Yang Sun, Yan, Dan Yao, Yan, Hua Zhu, and Jun Wang. "ScFv, Decorated PEG-PLA Based Nanoparticles for Enhanced siRNA Delivery to Her2+ Breast Cancer." Advanced healthcare materials (2014). http://onlinelibrary.wiley.com/doi/10.1002/adhm.201400037/full

“Keywords:siRNA delivery;single-chain antibody fragment;Her2;tumor targeting;breast cancer Abstract: Patients with Her2-overexpressing (Her2+) breast cancers generally have a poorer prognosis due to the high aggressiveness and chemoresistance of the disease. Small interfering RNA (siRNA) targeting the gene encoding polo-like kinase 1 (Plk1; siPlk1) has emerged as an efficient therapeutic agent for Her2+ breast cancers. Poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-PLA)-based nanoparticles for siRNA delivery were previously developed and optimized. In this study, for targeted delivery of siPlk1 to Her2+ breast cancer, anti-Her2 single-chain variable fragment antibody (ScFvHer2)-decorated PEG-PLA-based nanoparticles with si Plk1 encapsulation (ScFvHer2-NPsi Plk1) are developed. With the rationally designed conjugation site, ScFvHer2-NPsiRNA can specifically bind to the Her2 antigen overexpressed on the surface of Her2+ breast cancer cells. Therefore, ScFvHer2-NPsi Plk1 exhibits improved cellular uptake, promoted Plk1 silencing efficiency, and induced enhanced tumor cell apoptosis in Her2+ breast cancer cells, when compared with nontargeted NPsi Plk1. More importantly, ScFvHer2-NPsiRNA markedly enhances the accumulation of siRNA in Her2+ breast tumor tissue, and remarkably improves the efficacy of tumor suppression. Dose-dependent anti-tumor efficacy further demonstrates that ScFvHer2-decorated PEG-PLA-based nanoparticles with siPlk1 encapsulation can significantly enhance the inhibition of Her2+ breast tumor growth and reduce the dose of injected siRNA. These results suggest that ScFvHer2-decorated PEG-PLA-based nanoparticles show great potential for targeted RNA interference therapy of Her2+ breast tumor.”
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