ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrier
Abstract Background Oxidative stress acts as a trigger in the course of neurodegenerative diseases and neural injuries. An antioxidant-based therapy can be effective to ameliorate the deleterious effects of oxidative stress. Resveratrol (RSV) has been shown to be effective at removing excess reactiv...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-018-0340-7 |
| _version_ | 1798003579635630080 |
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| author | Yang Shen Bin Cao Noah R. Snyder Kevin M. Woeppel James R. Eles Xinyan Tracy Cui |
| author_facet | Yang Shen Bin Cao Noah R. Snyder Kevin M. Woeppel James R. Eles Xinyan Tracy Cui |
| author_sort | Yang Shen |
| collection | DOAJ |
| description | Abstract Background Oxidative stress acts as a trigger in the course of neurodegenerative diseases and neural injuries. An antioxidant-based therapy can be effective to ameliorate the deleterious effects of oxidative stress. Resveratrol (RSV) has been shown to be effective at removing excess reactive oxygen species (ROS) or reactive nitrogen species generation in the central nervous system (CNS), but the delivery of RSV into the brain through systemic administration is inefficient. Here, we have developed a RSV delivery vehicle based on polylactic acid (PLA)-coated mesoporous silica nanoparticles (MSNPs), conjugated with a ligand peptide of low-density lipoprotein receptor (LDLR) to enhance their transcytosis across the blood–brain barrier (BBB). Results Resveratrol was loaded into MSNPs (average diameter 200 nm, pore size 4 nm) at 16 μg/mg (w/w). As a gatekeeper, the PLA coating prevented the RSV burst release, while ROS was shown to trigger the drug release by accelerating PLA degradation. An in vitro BBB model with a co-culture of rat brain microvascular endothelial cells (RBECs) and microglia cells using Transwell chambers was established to assess the RSV delivery across BBB. The conjugation of LDLR ligand peptides markedly enhanced the migration of MSNPs across the RBECs monolayer. RSV could be released and effectively reduce the activation of the microglia cells stimulated by phorbol-myristate-acetate or lipopolysaccharide. Conclusions These ROS responsive LDLR peptides conjugated PLA-coated MSNPs have great potential for oxidative stress therapy in CNS. |
| first_indexed | 2024-04-11T12:09:58Z |
| format | Article |
| id | doaj.art-c43b3cd173c84067bf217cccba854f42 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T12:09:58Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-c43b3cd173c84067bf217cccba854f422022-12-22T04:24:38ZengBMCJournal of Nanobiotechnology1477-31552018-02-0116111710.1186/s12951-018-0340-7ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrierYang Shen0Bin Cao1Noah R. Snyder2Kevin M. Woeppel3James R. Eles4Xinyan Tracy Cui5Department of Bioengineering, University of PittsburghDepartment of Bioengineering, University of PittsburghDepartment of Bioengineering, University of PittsburghDepartment of Bioengineering, University of PittsburghDepartment of Bioengineering, University of PittsburghDepartment of Bioengineering, University of PittsburghAbstract Background Oxidative stress acts as a trigger in the course of neurodegenerative diseases and neural injuries. An antioxidant-based therapy can be effective to ameliorate the deleterious effects of oxidative stress. Resveratrol (RSV) has been shown to be effective at removing excess reactive oxygen species (ROS) or reactive nitrogen species generation in the central nervous system (CNS), but the delivery of RSV into the brain through systemic administration is inefficient. Here, we have developed a RSV delivery vehicle based on polylactic acid (PLA)-coated mesoporous silica nanoparticles (MSNPs), conjugated with a ligand peptide of low-density lipoprotein receptor (LDLR) to enhance their transcytosis across the blood–brain barrier (BBB). Results Resveratrol was loaded into MSNPs (average diameter 200 nm, pore size 4 nm) at 16 μg/mg (w/w). As a gatekeeper, the PLA coating prevented the RSV burst release, while ROS was shown to trigger the drug release by accelerating PLA degradation. An in vitro BBB model with a co-culture of rat brain microvascular endothelial cells (RBECs) and microglia cells using Transwell chambers was established to assess the RSV delivery across BBB. The conjugation of LDLR ligand peptides markedly enhanced the migration of MSNPs across the RBECs monolayer. RSV could be released and effectively reduce the activation of the microglia cells stimulated by phorbol-myristate-acetate or lipopolysaccharide. Conclusions These ROS responsive LDLR peptides conjugated PLA-coated MSNPs have great potential for oxidative stress therapy in CNS.http://link.springer.com/article/10.1186/s12951-018-0340-7Blood–brain barrier (BBB)Resveratrol (RSV)Mesoporous silica nanoparticles (MSNPs)Reactive oxygen species (ROS)LDLR ligand peptide |
| spellingShingle | Yang Shen Bin Cao Noah R. Snyder Kevin M. Woeppel James R. Eles Xinyan Tracy Cui ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrier Journal of Nanobiotechnology Blood–brain barrier (BBB) Resveratrol (RSV) Mesoporous silica nanoparticles (MSNPs) Reactive oxygen species (ROS) LDLR ligand peptide |
| title | ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrier |
| title_full | ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrier |
| title_fullStr | ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrier |
| title_full_unstemmed | ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrier |
| title_short | ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrier |
| title_sort | ros responsive resveratrol delivery from ldlr peptide conjugated pla coated mesoporous silica nanoparticles across the blood brain barrier |
| topic | Blood–brain barrier (BBB) Resveratrol (RSV) Mesoporous silica nanoparticles (MSNPs) Reactive oxygen species (ROS) LDLR ligand peptide |
| url | http://link.springer.com/article/10.1186/s12951-018-0340-7 |
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