Brain-targeting, acid-responsive antioxidant nanoparticles for stroke treatment and drug delivery.
A-BAM NPs, A-BAM NPs
ALT, alanine aminotransferase
AST, aspartate aminotransferase
Acid-triggered release
Antioxidant nanoparticles
BA, betulinic acid
BAM, betulinic amine
BBB, blood brain barrier
BIRDS, biosensor imaging of redundant deviation in shifts
BT, ß-sitosterol
DLS, dynamic light scattering
DTA, dehydrotrametenolic acid
DYDA, diketohydrindylidene diketohydrindamine
Drug delivery
GA, glycyrrhetic acid
Ischemic stroke
LCMS, liquid chromatography mass spectrometry
LP, lupeol
MCAO, middle cerebral artery occlusion
NA1
NMR, nuclear magnetic resonance
NP, nanoparticle
OA, oleanolic acid
PAA, poricoic acid
PEG, polyethylene glycol
SA, sumaresinolic acid
SEM, scanning electron microscopy
ST, stigmasterol
TEM, transmission electron microscope
TTC, triphenyltetrazolium chloride
UA, ursolic acid
tPA, tissue-type plasminogen activator
Journal
Bioactive materials
ISSN: 2452-199X
Titre abrégé: Bioact Mater
Pays: China
ID NLM: 101685294
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
22
11
2021
revised:
02
02
2022
accepted:
28
02
2022
entrez:
7
4
2022
pubmed:
8
4
2022
medline:
8
4
2022
Statut:
epublish
Résumé
Stroke is the leading cause of death and disability. Currently, there is no effective pharmacological treatment for this disease, which can be partially attributed to the inability to efficiently deliver therapeutics to the brain. Here we report the development of natural compound-derived nanoparticles (NPs), which function both as a potent therapeutic agent for stroke treatment and as an efficient carrier for drug delivery to the ischemic brain. First, we screened a collection of natural nanomaterials and identified betulinic acid (BA) as one of the most potent antioxidants for stroke treatment. Next, we engineered BA NPs for preferential drug release in acidic ischemic tissue through chemically converting BA to betulinic amine (BAM) and for targeted drug delivery through surface conjugation of AMD3100, a CXCR4 antagonist. The resulting AMD3100-conjugated BAM NPs, or A-BAM NPs, were then assessed as a therapeutic agent for stroke treatment and as a carrier for delivery of NA1, a neuroprotective peptide. We show that intravenous administration of A-BAM NPs effectively improved recovery from stroke and its efficacy was further enhanced when NA1 was encapsulated. Due to their multifunctionality and significant efficacy, we anticipate that A-BAM NPs have the potential to be translated both as a therapeutic agent and as a drug carrier to improve the treatment of stroke.
Identifiants
pubmed: 35386312
doi: 10.1016/j.bioactmat.2022.02.033
pii: S2452-199X(22)00109-8
pmc: PMC8958421
doi:
Types de publication
Journal Article
Langues
eng
Pagination
57-65Subventions
Organisme : NINDS NIH HHS
ID : R01 NS110721
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Informations de copyright
© 2022 The Authors.
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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