The Cervical and Meningeal Lymphatic Network as a Pathway for Retrograde Nanoparticle Transport to the Brain

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dc.contributor.authorRamos-Zaldivar, Hector
dc.contributor.authorPolakovicova, Iva
dc.contributor.authorSalas-Huenuleo, Edison
dc.contributor.authorYefi, Claudia P.
dc.contributor.authorSilva-Ancahuail, David
dc.contributor.authorJara-Guajardo, Pedro
dc.contributor.authorOyarzun, Juan Esteban
dc.contributor.authorNeira-Troncoso, Alvaro
dc.contributor.authorBurgos, Patricia, V
dc.contributor.authorCavieres, Viviana A.
dc.contributor.authorArias-Munoz, Eloisa
dc.contributor.authorMartinez, Carlos
dc.contributor.authorRiveros, Ana L.
dc.contributor.authorCorvalan, Alejandro H.
dc.contributor.authorKogan, Marcelo J.
dc.contributor.authorAndia, Marcelo E.
dc.date.accessioned2025-01-20T16:05:08Z
dc.date.available2025-01-20T16:05:08Z
dc.date.issued2024
dc.description.abstractIntroduction: The meningeal lymphatic vessels have been described as a pathway that transports cerebrospinal fluid and interstitial fluid in a unidirectional manner towards the deep cervical lymph nodes. However, these vessels exhibit anatomical and molecular characteristics typical of initial lymphatic vessels, with the absence of surrounding smooth muscle and few or absent valves. Given its structure, this network could theoretically allow for bidirectional motion. Nevertheless, it has not been assessed as a potential route for nanoparticles to travel from peripheral tissues to the brain. Methods: We employed superparamagnetic iron oxide nanoparticles (SPIONs), exosomes loaded with SPIONs, gold nanorods, and Chinese ink nanoparticles. SPIONs were prepared via chemical coprecipitation, while exosomes were isolated from the B16F10 melanoma cell line through the Exo-Spin column protocol and loaded with SPIONs through electroporation. Gold nanorods were functionalized with polyethylene glycol. We utilized C57BL/6 mice for post-mortem and in vivo procedures. To evaluate the retrograde directional flow, we injected each nanoparticle solution in the deep cervical lymph node. The head and neck were fixed for magnetic resonance imaging and histological analysis. Results: Here we show that extracellular vesicles derived from the B16F10 melanoma cell line, along with superparamagnetic iron oxide nanoparticles, gold nanorods, and Chinese ink nanoparticles can reach the meningeal lymphatic vessels and the brain of C57BL/6 mice after administration within the deep cervical lymph nodes post-mortem and in vivo, exclusively through lymphatic structures. Discussion: The functional anatomy of dural lymphatics has been found to be conserved between mice and humans, suggesting that our findings may have significant implications for advancing targeted drug delivery systems using nanoparticles. Understanding the retrograde transport of nanoparticles through the meningeal lymphatic network could lead to novel therapeutic approaches in nanomedicine, offering new insights into fluid dynamics in both physiological and neuropathological contexts. Further research into this pathway may unlock new strategies for treating neurological diseases or enhancing drug delivery to the brain.
dc.fuente.origenWOS
dc.identifier.doi10.2147/IJN.S477159
dc.identifier.issn1178-2013
dc.identifier.urihttps://doi.org/10.2147/IJN.S477159
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/89876
dc.identifier.wosidWOS:001342407500001
dc.language.isoen
dc.pagina.final10743
dc.pagina.inicio10725
dc.revistaInternational journal of nanomedicine
dc.rightsacceso restringido
dc.subjectextracellular vesicles
dc.subjectSPIONs
dc.subjectgold nanorods
dc.subjectChinese ink
dc.subjectmeningeal lymphatic vessels
dc.subjectnanomedicine
dc.titleThe Cervical and Meningeal Lymphatic Network as a Pathway for Retrograde Nanoparticle Transport to the Brain
dc.typeartículo
dc.volumen19
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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