Functionalized Nanomaterials Capable of Crossing the Blood-Brain Barrier

Shuai Zha, Haitao Liu, Hengde Li, Haolan Li, Ka-Leung Wong*, Angelo Homayoun All*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1820-1845
Number of pages26
JournalACS Nano
Issue number3
Early online date9 Jan 2024
Publication statusPublished - 23 Jan 2024

Scopus Subject Areas

  • Engineering(all)
  • Physics and Astronomy(all)
  • Materials Science(all)

User-Defined Keywords

  • BBB crossing
  • BBB receptor-mediated endocytosis
  • absorptive-mediated transcytosis
  • brain delivery
  • central nervous system delivery
  • functionalized nanomaterials
  • neurotheranostics
  • noninvasive BBB cargo delivery
  • receptor-mediated transcytosis


Dive into the research topics of 'Functionalized Nanomaterials Capable of Crossing the Blood-Brain Barrier'. Together they form a unique fingerprint.

Cite this