Reducible Bile Acid-Conjugated Polyethelenimine Nanoparticles Enhance Systemic siRNA Delivery to Solid Tumors
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초록
내용
Small interfering RNA (siRNA) gene silencing, also known as RNA interference, has been considered as a potential therapeutic strategy for targeting cancer therapy. In this study, a conjugate of the low molecular weight polyethylenimine (PEI), and deoxycholic acid (DA) was further modified with 4-fluorothiophenol (FTP) (TP-DA-PEI) to achieve systemic siRNA delivery. The thiophenol group would be involved with disulfide bonds between the polymer chains and siRNA modified with free thiols (thiol-siRNA) to form and π– π interactions between the pendent aromatic groups and coprostane ring of the bile acid. The TP-DA-PEI conjugates could form stable nanoparticles with thiol-siRNA. The TP-DA-PEI conjugate not only enhanced intracellular uptake, serum stability, and transfection efficiency, but also showed high accumulation of the polyplex nanoparticles and significant tumor growth inhibition effect in tumor-bearing mice after systemic administration.