Zwitterionic hyaluronic acid derivatives for co-delivery of both chemotherapeutic and nucleic acid drugs in breast cancer treatment

Traditionally, hyaluronic acid has been widely used for drug delivery, but the current application bottleneck is that hyaluronic acid is hydrophilic and electronegative, which makes it difficult to carry hydrophobic drugs and small interfering RNA (siRNA) with the same charge. Based on previous studies, we designed and synthesized hyaluronic acid nanocarriers HA-spermine/N,N,N-trimethylcystamine/DOX-TPP (HSTD) for loading siRNA to overcome the problem of siRNA release caused by strong electrostatic interaction. Then, N,N,N-trimethylcystamine in the carrier can be degraded by intracellular glutathione to completely and rapidly release siRNA, thus promoting transfection. Moreover, when co-delivered with the chemotherapy drug doxorubicin (DOX), this novel nanocarrier showed promising synergy in inhibiting tumor growth.