Use of single-site-functionalized PEG dendrons to prepare gene vectors that penetrate human mucus barriers.

Protective mucus layers serve as the body’s first line of defense at exposed surfaces of the eyes and respiratory, gastrointestinal, and cervicovaginal tracts. These highly viscoelastic and adhesive mucus gels trap most foreign pathogens and environmental ultrafine particles, which are then removed by mucus clearance mechanisms[1] (on the order of seconds to a few hours, depending on anatomical site). However, mucus also immobilizes and rapidly clears therapeutic nanoparticles, including synthetic drug carriers,[2] and clinically tested viral[3] and nonviral gene vectors[4] and, therefore, represents a critical obstacle to localized drug and gene delivery at mucosal surfaces for the treatment of a variety of diseases.[1b]