1. Dual-Porosity Hollow Nanoparticles for the Immunoprotection and Delivery of Nonhuman Enzymes
- Author
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Dmitri Simberg, William C. Trogler, Sadik C. Esener, Inanc Ortac, Jian Yang, Roger Y. Tsien, Ya san Yeh, and Bradley T. Messmer
- Subjects
Letter ,Materials science ,nonhuman enzymes ,enzyme encapsulation ,Nanoparticle ,Bioengineering ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,immune response ,Mice ,Bacillus cereus ,Bacterial Proteins ,Animals ,General Materials Science ,Porosity ,chemistry.chemical_classification ,Drug Carriers ,Mice, Inbred BALB C ,Nanoporous ,Nanoshells ,Mechanical Engineering ,technology, industry, and agriculture ,General Chemistry ,Penicillinase ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Small molecule ,Nanoshell ,0104 chemical sciences ,Nanomedicine ,Enzyme ,chemistry ,silica ,nanoparticles ,0210 nano-technology ,Drug carrier - Abstract
Although enzymes of nonhuman origin have been studied for a variety of therapeutic and diagnostic applications, their use has been limited by the immune responses generated against them. The described dual-porosity hollow nanoparticle platform obviates immune attack on nonhuman enzymes paving the way to in vivo applications including enzyme-prodrug therapies and enzymatic depletion of tumor nutrients. This platform is manufactured with a versatile, scalable, and robust fabrication method. It efficiently encapsulates macromolecular cargos filled through mesopores into a hollow interior, shielding them from antibodies and proteases once the mesopores are sealed with nanoporous material. The nanoporous shell allows small molecule diffusion allowing interaction with the large macromolecular payload in the hollow center. The approach has been validated in vivo using l-asparaginase to achieve l-asparagine depletion in the presence of neutralizing antibodies.
- Published
- 2014