Comparison of Biological Responses of Polymers Based on Imine and Disulfide Backbones for siRNA Delivery.

To achieve a successful delivery of siRNA by carriers in vivo, the degradation of polymers in response to tiny intracellular changes should be seriously considered. In addition, the balance between degradation and stability of polymers is another key point for high performance of carriers. In this study, imine and disulfide linkages, which are sensitive to pH changes and redox environment, respectively, were constructed as the main backbone of polymers to deliver siRNA at the intracellular and animal level. Comparisons were made between performances of these two different polymers. Both of the polymers synthesized here have good ability to condense siRNA. However, polyplexes formed by the imine backbone-based polymer (TPSP) showed a larger particle size and a higher zeta potential than that of the disulfide backbone-based polymer (DTDPS). Although both TPSP and DTDPS could deliver the target siRNA into 7721 cells, polyplexes formed by TPSP showed a higher silence efficiency in vitro and accomplished more accumulation in tumors. In conclusion, we believe TPSP is superior to be used for siRNA delivery and promises a potential for widespread use.