Premium
ScFv‐Decorated PEG‐PLA‐Based Nanoparticles for Enhanced siRNA Delivery to Her2 + Breast Cancer
Author(s) -
Dou Shuang,
Yang XianZhu,
Xiong MengHua,
Sun ChunYang,
Yao YanDan,
Zhu YanHua,
Wang Jun
Publication year - 2014
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201400037
Subject(s) - plk1 , gene silencing , small interfering rna , cancer research , breast cancer , rna interference , chemistry , peg ratio , apoptosis , cancer , microbiology and biotechnology , rna , medicine , biology , cell cycle , biochemistry , gene , finance , economics
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; si Plk1 ) 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 si Plk1 to Her2 + breast cancer, anti‐Her2 single‐chain variable fragment antibody (ScFv Her2 )‐decorated PEG‐PLA‐based nanoparticles with si Plk1 encapsulation (ScFv Her2 ‐NP si Plk1 ) are developed. With the rationally designed conjugation site, ScFv Her2 ‐NP siRNA can specifically bind to the Her2 antigen overexpressed on the surface of Her2 + breast cancer cells. Therefore, ScFv Her2 ‐NP si Plk1 exhibits improved cellular uptake, promoted Plk1 silencing efficiency, and induced enhanced tumor cell apoptosis in Her2 + breast cancer cells, when compared with nontargeted NP si Plk1 . More importantly, ScFv Her2 ‐NP siRNA 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 ScFv Her2 ‐decorated PEG‐PLA‐based nanoparticles with si Plk1 encapsulation can significantly enhance the inhibition of Her2 + breast tumor growth and reduce the dose of injected siRNA. These results suggest that ScFv Her2 ‐decorated PEG‐PLA‐based nanoparticles show great potential for targeted RNA interference therapy of Her2 + breast tumor.