journal article·2025Open access

Bola-amphiphilic glycodendrimers for targeting glial cells in the brain

Zhancun Bian, Wenzheng Zhang, Stefano Garofalo, Dinesh Dhumal, Junyue Zheng, Tom Roussel, Erik Laurini, Christina Galanakou, Clotilde Lauro, Marc Maresca, Yi Xia, Dandan Zhu, Sabrina Pricl, Xiaoxuan Liu, Cristina Limatola, Ling Peng

Nanoscale· Volume 17· Issue 48

Abstract

Targeting glial cells in the brain constitutes a formidable challenge due to the presence of the blood-brain barrier (BBB) and the difficulty in achieving specific targeting. Intranasal (IN) administration offers a promising solution to bypass the BBB for delivery directly to the brain, while nanotechnology-based delivery provides tailored targeting capabilities. Here, we report dendrimer-based nanosystems developed for IN administration to target astrocytes and microglia, two types of glial cells that play important roles in maintaining brain homeostasis. Specifically, we demonstrate that bola-amphiphilic glycodendrimers, Ia and Ib, which bear glucose and mannose terminals, respectively, target astrocytes and microglia in the mouse brain. These two glycodendrimers, composed of a hydrophobic bola-lipid in the middle connected with two hydrophilic poly(amidoamine) dendrons, were effectively synthesized via a click reaction using unprotected carbohydrate building units, and self-assembled into small and spherical nanoparticles by virtue of their amphiphilicity. In a mouse model, both dendrimer nanoparticles successfully reached the brain following IN administration, where the glucose-dendrimer Ia selectively targeted astrocytes and the mannose-dendrimer Ib targeted microglia. These findings highlight the potential of glycodendrimer-based nanosystems for precise targeting in the brain and offer a promising perspective for treating central nervous system (CNS) diseases.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Supramolecular Self-Assembly in Materials · Dendrimers and Hyperbranched Polymers · Chemical Synthesis and Analysis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Natural Medicines, Joint International Research Laboratory of Target Discovery and New Drug Innovation (Ministry of Education), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing, P. R. China

Aix Marseille University, CNRS, Center Interdisciplinaire de Nanoscience de Marseille, UMR 7325, “Equipe Labellisée Ligue Contre le Cancer”, Marseille, France

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, P. R. China

Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy

Aix Marseille Univ, CNRS, Centrale Med, ISM2, 13013 Marseille, France

Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS), DEA, University of Trieste, 34127 Trieste, Italy

Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland

IRCCS Neuromed, Pozzilli, Italy

Funding

Agence Nationale de la Recherche · National Key Research and Development Program of China · China Scholarship Council · Associazione Italiana per la Ricerca sul Cancro · NextGenerationEU

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