Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier
Open accessAbstract
The blood-brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, the BBB also prevents the passage of various forms of therapeutic agents, nanocarriers, and their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe and effective vehicles in neurotheranostics. In this Review, first we introduce the anatomical structure and physiological functions of the BBB. Second, we present the endogenous and exogenous transport mechanisms by which NPs cross the BBB. We report various forms of nanomaterials, carriers, and their cargos, with their detailed BBB uptake and permeability characteristics. Third, we describe the effect of regulating the size, shape, charge, and surface ligands of NPs that affect their BBB permeability, which can be exploited to enhance and promote neurotheranostics. We classify typical functionalized nanomaterials developed for BBB crossing. Fourth, we provide a comprehensive review of the recent progress in developing functional polymeric nanomaterials for applications in multimodal bioimaging, therapeutics, and drug delivery. Finally, we conclude by discussing existing challenges, directions, and future perspectives in employing functionalized nanomaterials for BBB crossing.
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Magnetic nanoparticles (MNPs) incorporate magnetic materials such as iron, cobalt, and nickel and exhibit magnetic behavior when exposed to magnetic fields.
“Magnetic nanoparticles (MNPs) are a class of NPs that incorporate magnetic materials, such as iron, cobalt, and nickel, and exhibit magnetic behavior when exposed to magnetic fields.”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [78]
The Exogenous Transport Mechanisms section (page not provided) describes MNPs with magnetic iron oxide cores and explains that external magnetic fields can move them. It does not identify cobalt or nickel as MNP materials, so the cited paper supports only part of the material list. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe success of the MNP strategy depends on the properties of the MNPs themselves, including size, magnetic properties, functionalization, and biocompatibility, as well as external factors.
“However, the success of the strategy also depends on the properties of the MNPs themselves, including size, magnetic properties, functionalization, and biocompatibility, as well as external factors [78].”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [78]
MNPs are composed of a magnetic core, most often magnetite (Fe3O4) or maghemite (α- or γ-Fe2O3), and a biocompatible surface.
“MNPs are composed of a magnetic core, most often magnetite, Fe3O4, or maghemite, α- or γ-Fe2O3, and a biocompatible surface [78].”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [78]
Inappropriate FUS conditions could result in transient inflammatory responses, flash edema, and even intracerebral hemorrhage.
“Therefore, inappropriate conditions could result in transient inflammatory responses, flash edema, and even intracerebral hemorrhage [78,80].”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [78]
The Exogenous Transport Mechanisms section describes FUS opening the blood–brain barrier and reports no hemorrhagic lesions in a small clinical study. A search of our copy for FUS-related inflammation, edema, and hemorrhage found no passage addressing whether inappropriate FUS conditions can cause the claimed complications. The stroke section discusses edema and inflammation in a different context. (LLM, conf=0.74)
Experimental — accuracy not yet measured
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- Authors
- Zha, S., Liu, H., Li, H., Li, H., Wong, K.-L., & All, A. H.
- Affiliations
- Hubei University of Chinese Medicine (CN)
- Hong Kong Baptist University (HK)
- Hong Kong Polytechnic University (HK)
- Corresponding author
- Wong, Ka-Leung
- All, Angelo Homayoun
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2024-01-09
- Volume
- 18
- Issue
- 3
- Pages
- 1820-1845
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- PMC
- PMC10811692
- OpenAlex
- W4390726995
- Cited by
- 378
- References
- 220
- Citations by year
- 2026: 162 · 2025: 164 · 2024: 52
- FWCI
- 19.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- ACS Nano (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Research Grants Council, University Grants Committee (12100121)
- Hong Kong Baptist University (21.4531.162640, 31.4531.179234)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- blood-brain barrier, functionalized nanomaterials, polymer nanomaterials, nanoparticle size and shape effects, surface ligands, blood-brain barrier permeability, brain drug delivery, multimodal bioimaging, nanocarriers
- MeSH terms
- Biological Transport, Blood-Brain Barrier, Brain, Drug Delivery Systems, Nanostructures, Nanoparticles
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