Among various enzyme-based therapies, enzyme-prodrug therapy (EPT) promises minimized side effects in that it activates non-toxic prodrugs locally where the enzymes are placed. The success of such an approach requires high enzyme stability against both structural denaturation and potential immunogenicity. This work examines the efficiency of nanoparticles for enzyme protection in EPT applications. Specifically, horseradish peroxidase (HRP)-encapsulated chitosan nanoparticles (HRP-CSNP) were constructed and examined with respect to stability enhancement. HRP-CSNP retained enzyme activity and had improved stability at 37 °C in the presence of a denaturant, urea. The nanoparticles effectively bound to the surface of human breast cancer cell Bcap37 and led to over 80 % cell death when applied with a prodrug indole-3-acetic acid.
Bibliographical noteFunding Information:
This work was supported by seed grant for cultivating and interdisciplinary research of Chinese Education Ministry, National Natural Science Foundation of China (21303050), China Postdoctoral Science Foundation Grant (2013M540341), and National ?Thousand Talents Program? of China.
© 2014, Springer Science+Business Media Dordrecht.
- Breast cancer
- Chitosan nanoparticles
- Enzyme-prodrug therapy
- Horseradish peroxidase
- Indole-3-acetic acid
- Nanoparticles for cancer therapy
- Protein stabilization