Engineering a Mesoporous Silicon Nanoparticle Cage to Enhance Performance of a Phosphotriesterase Enzyme for Degradation of VX Nerve Agent
Abstract The organophosphate (OP)‐hydrolyzing enzyme phosphotriesterase (PTE, variant L7ep‐3a) immobilized within a partially oxidized mesoporous silicon nanoparticle cage is synthesized and the catalytic performance of the enzyme@nanoparticle construct for hydrolysis of a simulant, dimethyl p‐nitro...
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409535 |
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| author | Yi‐Sheng Lu Eduardo Reynoso Moreno Yubin Huang Ruhan Fan Ashley T. Tucker Linnzi K. Wright Ronald A. Evans Brooke M. Ahern Donald E. Owens Stephen A. Chappell Dale J. Christensen John Dresios Michael J. Sailor |
| author_facet | Yi‐Sheng Lu Eduardo Reynoso Moreno Yubin Huang Ruhan Fan Ashley T. Tucker Linnzi K. Wright Ronald A. Evans Brooke M. Ahern Donald E. Owens Stephen A. Chappell Dale J. Christensen John Dresios Michael J. Sailor |
| author_sort | Yi‐Sheng Lu |
| collection | DOAJ |
| description | Abstract The organophosphate (OP)‐hydrolyzing enzyme phosphotriesterase (PTE, variant L7ep‐3a) immobilized within a partially oxidized mesoporous silicon nanoparticle cage is synthesized and the catalytic performance of the enzyme@nanoparticle construct for hydrolysis of a simulant, dimethyl p‐nitrophenyl phosphate (DMNP), and the live nerve agent VX is benchmarked against the free enzyme. In a neutral aqueous buffer, the optimized construct shows a ≈2‐fold increase in the rate of DMNP turnover relative to the free enzyme. Enzyme@nanoparticles with more hydrophobic surface chemistry in the interior of the pores show lower catalytic activity, suggesting the importance of hydration of the pore interior on performance. The enzyme@nanoparticle construct is readily separated from the neutralized agent; the nanoparticle is found to retain DMNP hydrolysis activity through seven decontamination/recovery cycles. The nanoparticle cage stabilizes the enzyme against thermal denaturing and enzymatic (trypsin) degradation conditions relative to free enzyme. When incorporated into a topical gel formulation, the PTE‐loaded nanoparticles show high activity toward the nerve agent VX in an ex vivo rabbit skin model. In vitro acetylcholinesterase (AChE) assays in human blood show that the enzyme@nanoparticle construct decontaminates VX, preserving the biological function of AChE when exposed to an otherwise incapacitating dose. |
| format | Article |
| id | doaj-art-86874606dd0748a4a99052ce21473bb2 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-86874606dd0748a4a99052ce21473bb22024-12-27T13:00:47ZengWileyAdvanced Science2198-38442024-12-011148n/an/a10.1002/advs.202409535Engineering a Mesoporous Silicon Nanoparticle Cage to Enhance Performance of a Phosphotriesterase Enzyme for Degradation of VX Nerve AgentYi‐Sheng Lu0Eduardo Reynoso Moreno1Yubin Huang2Ruhan Fan3Ashley T. Tucker4Linnzi K. Wright5Ronald A. Evans6Brooke M. Ahern7Donald E. Owens8Stephen A. Chappell9Dale J. Christensen10John Dresios11Michael J. Sailor12Department of Chemistry and Biochemistry University of California San Diego La Jolla CA 92093 USALeidos 10260 Campus Point Drive San Diego CA 92121 United StatesDepartment of Chemistry and Biochemistry University of California San Diego La Jolla CA 92093 USAMaterials Science and Engineering Program University of California San Diego La Jolla CA 92093 USALeidos 10260 Campus Point Drive San Diego CA 92121 United StatesUS Army Combat Capabilities Development Command Chemical Biological Center 8938 N Kings Creek Rd., E3150 Gunpowder MD 21010 USAUS Army Combat Capabilities Development Command Chemical Biological Center 8938 N Kings Creek Rd., E3150 Gunpowder MD 21010 USAUS Army Combat Capabilities Development Command Chemical Biological Center 8938 N Kings Creek Rd., E3150 Gunpowder MD 21010 USATFF Pharmaceuticals 1751 River Run Fort Worth TX 76107 USALeidos 10260 Campus Point Drive San Diego CA 92121 United StatesTFF Pharmaceuticals 1751 River Run Fort Worth TX 76107 USALeidos 10260 Campus Point Drive San Diego CA 92121 United StatesDepartment of Chemistry and Biochemistry University of California San Diego La Jolla CA 92093 USAAbstract The organophosphate (OP)‐hydrolyzing enzyme phosphotriesterase (PTE, variant L7ep‐3a) immobilized within a partially oxidized mesoporous silicon nanoparticle cage is synthesized and the catalytic performance of the enzyme@nanoparticle construct for hydrolysis of a simulant, dimethyl p‐nitrophenyl phosphate (DMNP), and the live nerve agent VX is benchmarked against the free enzyme. In a neutral aqueous buffer, the optimized construct shows a ≈2‐fold increase in the rate of DMNP turnover relative to the free enzyme. Enzyme@nanoparticles with more hydrophobic surface chemistry in the interior of the pores show lower catalytic activity, suggesting the importance of hydration of the pore interior on performance. The enzyme@nanoparticle construct is readily separated from the neutralized agent; the nanoparticle is found to retain DMNP hydrolysis activity through seven decontamination/recovery cycles. The nanoparticle cage stabilizes the enzyme against thermal denaturing and enzymatic (trypsin) degradation conditions relative to free enzyme. When incorporated into a topical gel formulation, the PTE‐loaded nanoparticles show high activity toward the nerve agent VX in an ex vivo rabbit skin model. In vitro acetylcholinesterase (AChE) assays in human blood show that the enzyme@nanoparticle construct decontaminates VX, preserving the biological function of AChE when exposed to an otherwise incapacitating dose.https://doi.org/10.1002/advs.202409535acetylcholinesterase activity assaydermal protectionenzyme immobilizationenzyme stabilityphosphotriesterase variant L7ep‐3a |
| spellingShingle | Yi‐Sheng Lu Eduardo Reynoso Moreno Yubin Huang Ruhan Fan Ashley T. Tucker Linnzi K. Wright Ronald A. Evans Brooke M. Ahern Donald E. Owens Stephen A. Chappell Dale J. Christensen John Dresios Michael J. Sailor Engineering a Mesoporous Silicon Nanoparticle Cage to Enhance Performance of a Phosphotriesterase Enzyme for Degradation of VX Nerve Agent Advanced Science acetylcholinesterase activity assay dermal protection enzyme immobilization enzyme stability phosphotriesterase variant L7ep‐3a |
| title | Engineering a Mesoporous Silicon Nanoparticle Cage to Enhance Performance of a Phosphotriesterase Enzyme for Degradation of VX Nerve Agent |
| title_full | Engineering a Mesoporous Silicon Nanoparticle Cage to Enhance Performance of a Phosphotriesterase Enzyme for Degradation of VX Nerve Agent |
| title_fullStr | Engineering a Mesoporous Silicon Nanoparticle Cage to Enhance Performance of a Phosphotriesterase Enzyme for Degradation of VX Nerve Agent |
| title_full_unstemmed | Engineering a Mesoporous Silicon Nanoparticle Cage to Enhance Performance of a Phosphotriesterase Enzyme for Degradation of VX Nerve Agent |
| title_short | Engineering a Mesoporous Silicon Nanoparticle Cage to Enhance Performance of a Phosphotriesterase Enzyme for Degradation of VX Nerve Agent |
| title_sort | engineering a mesoporous silicon nanoparticle cage to enhance performance of a phosphotriesterase enzyme for degradation of vx nerve agent |
| topic | acetylcholinesterase activity assay dermal protection enzyme immobilization enzyme stability phosphotriesterase variant L7ep‐3a |
| url | https://doi.org/10.1002/advs.202409535 |
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