With this hypothesis, Zhao et al. prepared CSHNs for the co-administration of hypoxiainducible factor 1α siRNA (HIF1α siRNA) and gemcitabine by the two-step method (double emulsion solvent evaporation technique). In this nanocarrier design, a mixture of mPEG-PLGA and cationic ε-polylysine was chosen as the polymeric core material for gemcitabine, which was coated with a mixture of DSPE-PEG -2000, lecithin, and cholesterol. Here, the cationic εpolylysine copolymer performs two tasks: building the polymeric core of the nanocarrier and effectively absorbing the negatively charged si-HIF1α on the surface through ionic interactions.