Histone-inspired biomimetic polymeric gene vehicles with excellent biocompatibility and enhanced transfection efficacy

Limited delivery options have hindered the development of nucleic acid drugs in clinical practice. Inspired by the natural DNA compressing ability of histones, herein we have synthesized novel polymeric carriers called PCA(m)H(n) designed to mimic the histone mechanism for gene delivery. These smart polymers, composed of cell penetrating guanidine groups and pH sensitive imidazole groups, exhibited superior transfection efficiency. Simultaneously, GSH-responsive degradation endowed PCA(m)H(n) with capabilities of real-time DNA release as well as timely biodegradation. In summary, these histone-inspired PCA(m)H(n) have shown a great potential in gene therapy.