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

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.