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The Olfactory Epithelium as a Gateway for Bloodborne Nanoparticles to the Central Nervous System

delete2025-11-08
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PRE
AI
M
M. B. Sharapova
K
Kseniia A Amelina
L
L. L. Kazakova
T
T. V. Ilchibaeva
D
Daniil Zuev
O
Olga I. Solovieva
K
Ksenia N. Morozova
Е
Елена Киселева
G
Gleb B. Sukhorukov
A
Alexander Victorovich Romashchenko
DOI：10.1039/D5BM01311Adelete
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Abstract

Abstract

En 中文
While transnasal nanoparticle (NP) mucosal uptake is well-documented; recent studies suggest that some NPs and viruses can also enter the central nervous system (CNS) through systemic circulation without disrupting blood-brain barrier (BBB) integrity. Here; we used T1-weighted MRI and optical tomography to track Mn3O4-NP and 130 nm polyelectrolyte capsules (LbL-Au) distribution in mouse brains following intravenous or intranasal administration. The olfactory epithelium (OE) serves as a critical gateway for blood-to-brain NP transport; mediating CNS entry through distinct intracellular and paracellular pathways. Pharmacological inhibition of axonal transport (colchicine; 10 μg/μl) and chemical ablation of the OE (ZnCl₂; 5%) completely blocked Mn3O4-NP accumulation in olfactory pathways (olfactory bulb; tract; and cortical targets; <5% of controls; p < 0.001); while permitting unaltered deposition in the adenohypophysis (92 ± 5% of control); confirming an olfactory neuron-dependent transport mechanism. In contrast; LbL-Au translocation was abolished by epithelial ablation but unaffected by axonal transport inhibition; demonstrating predominant paracellular passage. Notably; both intranasal and intravenous administration routes resulted in NP deposition within the OE and subsequent brain delivery; revealing route-independent olfactory uptake. These findings establish the OE as a dual-pathway hub for systemic NPs; facilitating CNS entry via intracellular axonal transport (Mn3O4-NPs; PtO-NPs) or paracellular mechanisms (LbL-Au). By demonstrating that blood-borne NPs can exploit olfactory pathways to bypass the BBB; this work challenges traditional models of CNS xenobiotic entry and opens new avenues for targeted neurotherapeutic delivery.

Journal

Biomaterials Science cover
Biomaterials Science
IF:
5.7
Papers:
4.8K
Citations:
2.1W

Organization

No organization information available