Nanoparticle-Mediated Drug Delivery to the Central Nervous System

Nanoparticle-mediated delivery has emerged as a transformative approach to transport therapeutic agents across the blood–brain barrier (BBB) and into the central nervous system (CNS). These systems, ranging from liposomes and solid lipid nanoparticles to polymeric nanogels and biomimetic carriers, offer tunable size, surface chemistry and mechanical properties to negotiate vascular and cellular barriers. Surface functionalisation with targeting ligands—such as apolipoprotein E, transferrin receptor antibodies or peptide motifs derived from viral proteins—enables receptor-mediated endocytosis into brain endothelium. Stimuli-responsive designs further permit on-demand drug release by light, pH or enzymatic cues. Beyond chemotherapeutic payloads, recent advances encompass nucleic acid vectors for gene silencing, contrast agents for combined diagnosis and therapy, and immunomodulatory cargos for synergistic tumour eradication. Preclinical models of glioblastoma, Alzheimer’s disease and viral encephalitis have demonstrated enhanced survival, plaque reduction and neuroprotection. Ongoing efforts focus on optimising pharmacokinetics, minimising off-target effects and scaling manufacture under clinical-grade conditions. The convergence of materials science, neurobiology and immunology promises to unlock new treatments for hitherto intractable CNS disorders.

Research from Nature Portfolio

Recent studies have demonstrated a short peptide derived from viral glycoprotein that, when conjugated to arginine-rich sequences, binds neuronal receptors and enables non-invasive transvascular delivery of small interfering RNA for effective gene silencing in the brain. More recently, near-infrared-activatable biomimetic nanogels, fashioned from crosslinked polysaccharide and polyacid cores and camouflaged with apolipoprotein E-decorated erythrocyte membrane, have been shown to traverse the BBB under targeted irradiation and release chemotherapeutic agents deep within orthotopic glioblastoma lesions. Foundational work has also explored interleukin-13 receptor α2-targeted copolymer nanoparticles loaded with paclitaxel, achieving enhanced specificity to glioma cells, improved intracranial accumulation and prolonged survival in preclinical glioblastoma models.

Nanoparticle-Mediated Drug Delivery to the Central Nervous System publication trend

The graph below shows the total number of articles in nanoparticle-mediated drug delivery to the central nervous system across all publications each year (not limited to Nature Index journals).

Technical terms

Blood–brain barrier (BBB): A selective endothelial interface that restricts passage of most molecules from the bloodstream into the CNS.

Liposomes: Spherical vesicles composed of one or more phospholipid bilayers used to encapsulate hydrophilic and lipophilic drugs.

Solid lipid nanoparticles: Submicron carriers formed from solid lipids, providing controlled release and enhanced stability of encapsulated agents.

Biomimetic nanogel: Hydrated, crosslinked polymer networks engineered to mimic biological membranes for enhanced biocompatibility and cargo release.

Receptor-mediated endocytosis: Cellular uptake mechanism triggered by the binding of targeting ligands on nanoparticles to specific cell-surface receptors.

Stimuli-responsive system: Nanoparticles designed to undergo physical or chemical changes in response to external triggers such as light, pH or enzymes.

Surface functionalisation: Chemical modification of nanoparticle surfaces to attach targeting moieties or stealth coatings to modulate biodistribution and cellular interactions.

References

1. Nucleic acid drug vectors for diagnosis and treatment of brain diseases. Signal Transduction and Targeted Therapy (2023).
2. Engineered apoptotic bodies hitchhiking across the blood-brain barrier achieved a combined photothermal-chemotherapeutic effect against glioma. Theranostics (2023).
3. Transvascular delivery of small interfering RNA to the central nervous system. Nature (2007).
4. Near infrared-activatable biomimetic nanogels enabling deep tumor drug penetration inhibit orthotopic glioblastoma. Nature Communications (2022).
5. Improved anti-glioblastoma efficacy by IL-13Rα2 mediated copolymer nanoparticles loaded with paclitaxel. Scientific Reports (2015).
6. Brain co‐delivery of first‐line chemotherapy drug and epigenetic bromodomain inhibitor for multidimensional enhanced synergistic glioblastoma therapy. Exploration (2022).