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Cited by 40RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryBarrier Structure and Function Studies

Nonviral nanoparticle gene delivery into the CNS for neurological disorders and brain cancer applications

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Yang, Joanna, Luly, Kathryn M., Green, Jordan J.·2023·WIREs Nanomedicine and Nanobiotechnology
DOI 10.1002/wnan.1853PMC PMC10023321
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Abstract

Nonviral nanoparticles have emerged as an attractive alternative to viral vectors for gene therapy applications, utilizing a range of lipid‐based, polymeric, and inorganic materials. These materials can either encapsulate or be functionalized to bind nucleic acids and protect them from degradation. To effectively elicit changes to gene expression, the nanoparticle carrier needs to undergo a series of steps intracellularly, from interacting with the cellular membrane to facilitate cellular uptake to endosomal escape and nucleic acid release. Adjusting physiochemical properties of the nanoparticles, such as size, charge, and targeting ligands, can improve cellular uptake and ultimately gene delivery. Applications in the central nervous system (CNS; i.e., neurological diseases, brain cancers) face further extracellular barriers for a gene‐carrying nanoparticle to surpass, with the most significant being the blood–brain barrier (BBB). Approaches to overcome these extracellular challenges to deliver nanoparticles into the CNS include systemic, intracerebroventricular, intrathecal, and intranasal administration. This review describes and compares different biomaterials for nonviral nanoparticle‐mediated gene therapy to the CNS and explores challenges and recent preclinical and clinical developments in overcoming barriers to nanoparticle‐mediated delivery to the brain. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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  • Therapies for brain tumors, cerebrovascular diseases, and neurodegenerative diseases are limited because of a lack of effective methods to enable drugs to surpass natural protective hindrances and enter the central nervous system.

    “However, therapies for these challenging diseases are limited, because of the lack of effective methods, to enable drugs surpass natural protective hindrances to maintain homeostasis within the brain for preventing the entry of drug molecules to the CNS.133”

    From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [133]

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200 of 265 shown

Cited by

Sorted by citations

Authors
Yang, J., Luly, K. M., & Green, J. J.
Affiliations
Johns Hopkins University (US)
ORCID
Venue
WIREs Nanomedicine and Nanobiotechnology
Publisher
Wiley
Published
2022-10-03
Volume
15
Issue
2
Pages
e1853-e1853
ISSN
  • 1939-0041 (ISSN-L)
  • 1939-5116
DOI
10.1002/wnan.1853
PMC
PMC10023321
OpenAlex
W4301391706
Cited by
40
References
16
Citations by year
2026: 14 · 2025: 15 · 2024: 7 · 2023: 4
FWCI
0.68
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R01CA228133)
  • National Institute of Biomedical Imaging and Bioengineering (P41EB028239)
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
gene delivery, central nervous system, blood-brain barrier, neurological disorders, brain cancer, gene therapy, lipid nanoparticles, polymeric nanoparticles, inorganic nanoparticles, endosomal escape, cellular uptake, intranasal drug delivery, intrathecal drug delivery, intracerebroventricular administration, systemic drug delivery
MeSH terms
Blood-Brain Barrier, Brain, Brain Neoplasms, Central Nervous System, Humans, Genetic Therapy, Drug Delivery Systems, Nanoparticles

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