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dc.contributor.authorZhang, Shenqi
dc.contributor.authorPeng, Bin
dc.contributor.authorChen, Zeming
dc.contributor.authorYu, Jiang
dc.contributor.authorDeng, Gang
dc.contributor.authorBao, Youmei
dc.contributor.authorMa, Chao
dc.contributor.authorDu, Fengyi
dc.contributor.authorSheu, Wendy C.
dc.contributor.authorKimberly, W. Taylor
dc.contributor.authorSimard, J. Marc
dc.contributor.authorComan, Daniel
dc.contributor.authorChen, Qianxue
dc.contributor.authorHyder, Fahmeed
dc.contributor.authorZhou, Jiangbing
dc.contributor.authorSheth, Kevin N.
dc.date.accessioned2022-03-16T12:26:26Z
dc.date.available2022-03-16T12:26:26Z
dc.date.issued2022-01-01
dc.identifier.urihttp://hdl.handle.net/10713/18271
dc.description.abstractStroke 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. © 2022 The Authorsen_US
dc.description.sponsorshipNational Institutes of Healthen_US
dc.description.urihttps://doi.org/10.1016/j.bioactmat.2022.02.033en_US
dc.language.isoenen_US
dc.publisherKeAi Communications Co.en_US
dc.relation.ispartofBioactive Materialsen_US
dc.subjectAcid-triggered releaseen_US
dc.subjectAntioxidant nanoparticlesen_US
dc.subjectDrug deliveryen_US
dc.subjectIschemic strokeen_US
dc.subjectNA1en_US
dc.titleBrain-targeting, acid-responsive antioxidant nanoparticles for stroke treatment and drug deliveryen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.bioactmat.2022.02.033
dc.source.journaltitleBioactive Materials


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