TEMPO radical-functionalized amphiphilic dendritic structures as metal-free MRI contrast agents from fibers to nanoparticles

The pursuit of alternatives to gadolinium-based contrast agents for MRI is crucial to mitigate their known toxicity. Radical dendrimers (i.e. dendrimers fully functionalized with organic radicals), have emerged as promising substitutes due to their paramagnetic properties and demonstrated low toxici...

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Detalles Bibliográficos
Autores: Zhang, Songbai, Lloveras, Vega, Wu, Yufei, Vidal Gancedo, José
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::87baa9bb4d9f819556529247fd1e75e4
Acceso en línea:http://hdl.handle.net/10261/431769
https://api.elsevier.com/content/abstract/scopus_id/85214508138
Access Level:acceso embargado
Palabra clave:Contrast agents
Dendrimers
MRI
Organic radicals
Self-assembly
Descripción
Sumario:The pursuit of alternatives to gadolinium-based contrast agents for MRI is crucial to mitigate their known toxicity. Radical dendrimers (i.e. dendrimers fully functionalized with organic radicals), have emerged as promising substitutes due to their paramagnetic properties and demonstrated low toxicity both in vitro and in vivo. However, achieving water solubility in radical-containing macromolecules remains an important challenge. In this study, we propose the development of nanoparticle-based contrast agents through the self-assembly of amphiphilic dendritic-linear-dendritic structures. We synthesized and characterized a series of triblock copolymers comprising bis(hydroxymethyl)propionic acid based dendrons functionalized with TEMPO radicals at both ends of a PEG20k chain. Specifically, we extensively investigated the self-assembly behavior of generation 2 (G2) amphiphilic radical dendritic structure featuring 8 branches functionalized with TEMPO radicals. Our findings revealed distinct morphological characteristics and colloidal stability profiles depending on the assembly method. Organic nanoparticles formed from G2 species exhibited a homogeneous spherical morphology with low polydispersion and high stability upon time and dilution. However, G2 species directly dissolved in water tended to form fibers, showing high polydispersion and low stability. The different supramolecular structures adopted by the G2 amphiphilic radical dendritic structure appeared to influence their relaxivity, with slightly enhanced relaxivity observed in the case of well-formed homogeneous and rigid spherical nanoparticles. The favorable relaxivity values achieved, coupled with the observed absence of cytotoxicity and the straightforward synthesis process, indicate a promising avenue for advancing completely organic metal-free contrast agents built upon amphiphilic dendritic structures.