Degradation behavior of silk nanoparticles – enzyme responsiveness

Thidarat Wongpinyochit, Blair F. Johnston, F. Philipp Seib

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)
34 Downloads (Pure)


Silk nanoparticles are viewed as promising vectors for intracellular drug delivery as they can be taken up into cells by endocytosis and trafficked to lysosomes, where lysosomal enzymes and the low pH trigger payload release. However, the subsequent degradation of the silk nanoparticles themselves still requires study. Here, we report the responsiveness of native and PEGylated silk nanoparticles to degradation following exposure to proteolytic enzymes (protease XIV and α-chymotrypsin) and papain, a cysteine protease. Both native and PEGylated silk nanoparticles showed similar degradation behavior over a 20 day exposure period (degradation rate: protease XIV > papain >> chymotrypsin). Within 1 day, the silk nanoparticles were rapidly degraded by protease XIV, resulting in a ~50% mass loss, an increase in particle size, and a reduction in the amorphous content of the silk secondary structure. By contrast, 10 days of papain treatment was necessary to observe any significant change in nanoparticle properties, and chymotrypsin treatment had no effect on silk nanoparticle characteristics over the 20-day study period. Silk nanoparticles were also exposed ex vivo to mammalian lysosomal enzyme preparations to mimic the complex lysosomal microenvironment. Preliminary results indicated a 45% reduction in the silk nanoparticle size over a 5-day exposure. Overall, the results demonstrate that silk nanoparticles undergo enzymatic degradation, but the extent and kinetics are enzyme specific.
Original languageEnglish
Pages (from-to)942-951
Number of pages10
JournalACS Biomaterials Science & Engineering
Issue number3
Early online date7 Feb 2018
Publication statusE-pub ahead of print - 7 Feb 2018


  • silk nanoparticles
  • biodegradation
  • proteolytic enzymes
  • ex vivo lysosomal enzymes


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