pH-sensitive zwitterionic polycarboxybetaine as a potential non-viral vector for small interfering RNA delivery

Abstract

Small interfering RNA (siRNA) has great potential for the treatment of various diseases. However, its intrinsic deficiencies seriously limit its application. Herein, pH-sensitive zwitterionic polymer polycarboxybetaine (PCB) was developed as a non-viral vector for siRNA. The PCB could be protonated in an acidic environment and become positively charged from a cancer site. After protonation, PCB could complex siRNA via electrostatic interaction, and its loading ability was enhanced with a decrease of pH value. Compared with the PEI 10k, PCB₅₀ with a similar molecular weight had comparable siRNA loading ability and lower cytotoxicity. Besides, siRNA loaded by PCB₅₀ could escape from endosomes and reduce the loss of drugs, and based on the excellent uptake and obvious apoptotic effect on HeLa cells, the pH-sensitive PCB with low cytotoxicity could be used as a non-viral vector for safe siRNA delivery for cancer treatment.