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 drug...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,Ntrimethylcystamine in the carrier can be degraded by intracellular glutathione to completely and rapidly release siRNA,thus promoting transfection.Moreover,when codelivered with the chemotherapy drug doxorubicin(DOX),this novel nanocarrier showed promising synergy in inhibiting tumor growth.展开更多
基金supported by the National Key Research and Development Program of China(No.2022YFE0107800)National Natural Science Foundation of China(Nos.82373206,and 82073332)Zhejiang Provincial Natural Science Foundation of China(No.LHDMZ24H300002)。
文摘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,Ntrimethylcystamine in the carrier can be degraded by intracellular glutathione to completely and rapidly release siRNA,thus promoting transfection.Moreover,when codelivered with the chemotherapy drug doxorubicin(DOX),this novel nanocarrier showed promising synergy in inhibiting tumor growth.