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Cited by 42RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryBarrier Structure and Function Studies

Functionalized nanoparticles to deliver nucleic acids to the brain for the treatment of Alzheimer’s disease

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Muolokwu, Chinenye Edith, Chaulagain, Bivek, Gothwal, Avinash, Mahanta, Arun Kumar, Tagoe, Benjamin, Lamsal, Babita, Singh, Jagdish·2024·Frontiers in Pharmacology
DOI 10.3389/fphar.2024.1405423PMC PMC11157074
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Abstract

Brain-targeted gene delivery across the blood-brain barrier (BBB) is a significant challenge in the 21st century for the healthcare sector, particularly in developing an effective treatment strategy against Alzheimer’s disease (AD). The Internal architecture of the brain capillary endothelium restricts bio-actives entry into the brain. Additionally, therapy with nucleic acids faces challenges like vulnerability to degradation by nucleases and potential immune responses. Functionalized nanocarrier-based gene delivery approaches have resulted in safe and effective platforms. These nanoparticles (NPs) have demonstrated efficacy in protecting nucleic acids from degradation, enhancing transport across the BBB, increasing bioavailability, prolonging circulation time, and regulating gene expression of key proteins involved in AD pathology. We provided a detailed review of several nanocarriers and targeting ligands such as cell-penetrating peptides (CPPs), endogenous proteins, and antibodies. The utilization of functionalized NPs extends beyond a singular system, serving as a versatile platform for customization in related neurodegenerative diseases. Only a few numbers of bioactive regimens can go through the BBB. Thus, exploring functionalized NPs for brain-targeted gene delivery is of utmost necessity. Currently, genes are considered high therapeutic potential molecules for altering any disease-causing gene. Through surface modification, nanoparticulate systems can be tailored to address various diseases by replacing the target-specific molecule on their surface. This review article presents several nanoparticulate delivery systems, such as lipid NPs, polymeric micelles, exosomes, and polymeric NPs, for nucleic acids delivery to the brain and the functionalization strategies explored in AD research.

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Cited by

Sorted by citations

Authors
Muolokwu, C. E., Chaulagain, B., Gothwal, A., Mahanta, A. K., Tagoe, B., Lamsal, B., & Singh, J.
Affiliations
North Dakota State University (US)
Corresponding author
Singh, Jagdish
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2024-05-24
Volume
15
Pages
1405423-1405423
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2024.1405423
PMC
PMC11157074
OpenAlex
W4398773846
Cited by
42
References
13
Citations by year
2026: 23 · 2025: 16 · 2024: 3
FWCI
1.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health (RF1 AG068034 RF1 AG068034-01A1S1 R01 AG08398)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
Alzheimer's disease, blood-brain barrier, functionalized nanoparticles, nucleic acid delivery, cell-penetrating peptides, antibody targeting, exosomes, polymeric micelles, lipid nanoparticles, polymeric nanoparticles, surface modification, neurodegenerative diseases, gene therapy

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