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J Nanobiotechnology. 2018 Feb 13;16(1):13. doi: 10.1186/s12951-018-0340-7.

ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood-brain barrier.

Author information

1
Department of Bioengineering, University of Pittsburgh, 5057 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, PA, 15260, USA.
2
Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China.
3
Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
4
Department of Bioengineering, University of Pittsburgh, 5057 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, PA, 15260, USA. xic11@pitt.edu.
5
Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, 15260, USA. xic11@pitt.edu.
6
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA. xic11@pitt.edu.

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.

KEYWORDS:

Blood–brain barrier (BBB); LDLR ligand peptide; Mesoporous silica nanoparticles (MSNPs); Reactive oxygen species (ROS); Resveratrol (RSV)

PMID:
29433522
PMCID:
PMC5810018
DOI:
10.1186/s12951-018-0340-7
[Indexed for MEDLINE]
Free PMC Article

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