ScFv‐Decorated PEG‐PLA‐Based Nanoparticles for Enhanced siRNA Delivery to Her2+ Breast Cancer. Issue 11 (20th June 2014)

• Record Type: Journal Article
• Authors: Dou, Shuang; Yang, Xian‐Zhu; Xiong, Meng‐Hua; Sun, Chun‐Yang; Yao, Yan‐Dan; Zhu, Yan‐Hua; Wang, Jun
• Is Part Of: Advanced healthcare materials. Volume 3:Issue 11(2014:Nov.)
• Page Start: 1792
• Page End: 1803
• Publication Date: 2014-06-20
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201400037
• Languages: English
• ISSNs: 2192-2640

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Patients with Her2‐overexpressing (Her2<sup>+</sup>) 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; si<italic>Plk1</italic>) has emerged as an efficient therapeutic agent for Her2<sup>+</sup> breast cancers. Poly(ethylene glycol)‐<italic>block</italic>‐poly(<sc>d, l</sc>‐lactide) (PEG‐PLA)‐based nanoparticles for siRNA delivery were previously developed and optimized. In this study, for targeted delivery of si<italic>Plk1</italic> to Her2<sup>+</sup> breast cancer, anti‐Her2 single‐chain variable fragment antibody (ScFv<sub>Her2</sub>)‐decorated PEG‐PLA‐based nanoparticles with si <italic>Plk1</italic> encapsulation (ScFv<sub>Her2</sub>‐NP<sub>si <italic>Plk1</italic></sub>) are developed. With the rationally designed conjugation site, ScFv<sub>Her2</sub>‐NP<sub>siRNA</sub> can specifically bind to the Her2 antigen overexpressed on the surface of Her2<sup>+</sup> breast cancer cells. Therefore, ScFv<sub>Her2</sub>‐NP<sub>si <italic>Plk1</italic></sub> exhibits improved cellular uptake, promoted Plk1 silencing efficiency, and induced enhanced tumor cell apoptosis in Her2<sup>+</sup> breast cancer cells, when compared with nontargeted NP<sub>si <italic>Plk1</italic></sub>. More importantly, ScFv<sub>Her2</sub>‐NP<sub>siRNA</sub> markedly enhances the accumulation of siRNA in Her2<sup>+</sup> breast tumor tissue, and remarkably improves the efficacy of tumor suppression. Dose‐dependent anti‐tumor efficacy further demonstrates that ScFv<sub>Her2</sub>‐decorated PEG‐PLA‐based nanoparticles with si<italic>Plk1</italic> encapsulation can significantly enhance the inhibition of Her2<sup>+</sup> breast tumor growth and reduce the dose of injected siRNA. These results suggest that ScFv<sub>Her2</sub>‐decorated PEG‐PLA‐based nanoparticles show great potential for targeted RNA interference therapy of Her2<sup>+</sup> breast tumor.</p> </abstract>