Abstract

Silk nanofibers are versatile carriers for hydrophobic and hydrophilic drugs, but fall short in terms of effective delivery to cells, which is essential for therapeutic benefits. Here, the size of silk nanofibers was tuned by ultrasonic treatment to improve the cell penetration features without impacting the structural features. The gradual decrease in silk nanofiber length from 1700 to 40 nm resulted in improved cell uptake. The internalized silk nanofiber carriers evaded lysosomes, which facilitated retention in cancer cells in vitro. The smaller sizes also facilitated enhanced penetration of tumor spheroids for improved delivery in vitro. The cytotoxicity of paclitaxel (PTX)-laden nanocarriers increased when the length of the silk nanocarriers decreased. Both the drug loading capacity and delivery of silk nanocarriers with optimized sizes suggest potential utility in cell treatments.