In human airway epithelium possessing additional extracellular barriers such as mucus layers, transfection using conventional lipid-based or positively charged carriers is extremely limited. In the mucus layer, dense mucin fibers and negatively charged proteoglycans provide the adhesive and viscous protective layer that often trap and remove positively charged carriers, resulting in poor delivery of payloads to the underlying epithelial cells. Because understanding on the genetic and molecular changes upon external stimuli or viral infections is pivotal to develop proper preventive or therapeutic tools by controlling the gene expressions, developing a novel delivery material that overcomes the biological barrier is highly needed. Here, we report a direct chemical modulation technique that introduces hydrophilic group at the guanidine group via guanylurea bond formation. Guanylurea side chain-containing conjugated polymers (CPs) exhibit an efficient knockdown of a target gene in well-differentiated primary normal human bronchial epithelium (NHBE) cells, while conventional lipid-based and positively charged carriers exhibit no or very poor transfection efficiency. Because the primary culture of NHBE cells reproduces the in vivo morphology and key physiologic processes to regenerate the native human bronchial epithelium, the transfection efficacy demonstrated in this report can be reasonably correlated to real in vivo environment.

Guanylurea-functionalized conjugated polymers for efficient gene knockdown in normal human bronchial epithelium cells

2019 Spring National Meeting

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