Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 4, Issue 3, Pages 942-951Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.7b01021
Keywords
silk nanoparticles; biodegradation; proteolytic enzymes; ex vivo lysosomal enzymes
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Funding
- Marie Curie Action Career Integration Grant within the seventh European Union Framework Program [334134]
- University of Strathclyde
- Nanyang Technological University, Singapore
- EPSRC Future Continuous Manufacturing and Advanced Crystallization (CMAC) Research Hub [EP/P006965/1]
- U.K. Research Partnership Fund award from the Higher Education Funding Council for England [HH13054]
- EPSRC [EP/P006965/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/P006965/1] Funding Source: researchfish
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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 alpha-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 >> alpha-chymotrypsin). Within 1 day, the silk nanoparticles were rapidly degraded by protease XIV, resulting in a similar to 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 alpha-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.
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