Surface-charge-engineered magnetic silk fibroin nanocarriers for pH-responsive 5-fluorouracil delivery and in vitro magnetic localization.

Surface-charge engineering offers a simple strategy to tune magnetic nanocarriers for anticancer drug delivery. In this study, silk fibroin/Fe3O4 nanocarriers (DMSs) were prepared by assembling silk fibroin (SF) with carboxyl- or amine-functionalized Fe3O4 cores and loaded with 5-fluorouracil (5-FU). The two formulations showed opposite surface charges, nanoscale dimensions, preserved superparamagnetism, comparable drug-loading contents of 5.84% and 5.92%, and distinct silk fibroin matrix organizations. DMSs-COOH formed a relatively compact β-sheet-rich matrix, whereas DMSs-NH2+ showed a more favorable acid-responsive release behavior. Compared with free 5-FU, both DMSs suppressed burst release and enabled sustained release. DMSs-NH2+ produced the strongest inhibition of 4T1 cells at 24 h. Both rhodamine B-labeled DMSs were internalized by 4T1 cells, magnetically retained in an in vitro flow model, and showed hemolysis rates below 3%. These findings support magnetic-core surface charge as a useful parameter for tuning SF/Fe3O4 nanocarriers, although size optimization and in vivo validation are still required.