Effective and Specific Gene Silencing of Epidermal Growth Factor Receptors Mediated by Conjugated Oxaborole and...

Oxaborole-based polymers are stimuli-responsive materials that can reversibly interact with diols at pH values higher than their pK_a. The strong binding of the oxaborole with cis-hydroxyl groups allow rapid cross-linking of the polymer chains. In this study, we exploited this phenomenon to develop a novel delivery system for the complexation, protection, and delivery of epidermal growth factor receptors (EGFR) siRNA (small interfering RNA). Galactose and oxaborole polymers were first synthesized by the reversible addition-fragmentation chain transfer (RAFT) process, and they were found to show a robust interaction with each other via the oxaborole-diol effect, which allowed the formation of stable polyplexes with siRNA. Although complexes were successfully formed between the neutral galactose and oxaborole-based polymers, these complexes were insufficient in the protection of the siRNA. Therefore, cationic glycopolymers and oxaborole polymers were investigated showing superior complexation with siRNA and exhibiting effective gene silencing in HeLa (cervical) cancer cells, while showing low toxicity. Gene silencing of up to 60% was achieved with these new complexes in the presence and absence of serum. The excellent stability of the complexes under physiological conditions and the observed low cytotoxicity 48 h post-transfection demonstrated the high potential of this new system for gene silencing therapy application in clinics.