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| Home > Articles > Published articles > Metal-Free Radical Dendrimers as MRI Contrast Agents for Glioblastoma Diagnosis : |
| Home > Articles > Published articles > Metal-Free Radical Dendrimers as MRI Contrast Agents for Glioblastoma Diagnosis : |
(Institut de Ciència de Materials de Barcelona) (Instituto de Salud Carlos III) (Universitat Autònoma de Barcelona. Servei de Ressonància Magnètica Nuclear) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Institut de Ciència de Materials de Barcelona)
| Date: | 2022 |
| Abstract: | Simultaneously being a nonradiative and noninvasive technique makes magnetic resonance imaging (MRI) one of the highly required imaging approaches for the early diagnosis and follow-up of tumors, specifically for brain cancer. Paramagnetic gadolinium (Gd)-based contrast agents (CAs) are the most widely used ones in brain MRI acquisitions with special interest when assessing blood-brain barrier (BBB) integrity, a characteristic of high-grade tumors. However, alternatives to Gd-based contrast agents (CAs) are highly required to overcome their established toxicity. Organic radicals anchored on a dendrimer macromolecule surface (radical dendrimers) are promising alternatives since they also exhibit paramagnetic properties and can act as T CAs like Gd-based CAs while being organic species (mitigating concerns about toxic metal accumulation). Here, we studied the third generation of a water-soluble family of poly(phosphorhydrazone) radical dendrimers, with 48 PROXYL radical units anchored on their branches, exploring their potential of ex vivo and in vivo contrast enhancement in brain tumors (in particular, of immunocompetent, orthotopic GL261 murine glioblastoma (GB)). Remarkably, this radical species provides suitable contrast enhancement on murine GL261 GB tumors, which was comparable to that of commercial Gd-based CAs (at standard dose 0. 1 mmol/kg), even at its 4 times lower administered dose (0. 025 mmol/kg). Importantly, no signs of toxicity were detected in vivo. In addition, it showed a selective accumulation in brain tumor tissues, exhibiting longer retention within the tumor, which allows performing imaging acquisition over longer time frames (≥2. 5 h) as opposed to Gd chelates. Finally, we observed high stability of the radicals in biological media, on the order of hours instead of minutes, characteristic of the isolated radicals. All of these features allow us to suggest that the G3-Tyr-PROXYL-ONa radical dendrimer could be a viable alternative to metal-based MRI contrast agents, particularly on MRI analysis of GB, representing, to the best of our knowledge, the first case of organic radical species used for this purpose and one of the very few examples of these types of radical species working as MRI CAs in vivo. |
| Grants: | Agencia Estatal de Investigación PID2019-105622RB-I00 Agencia Estatal de Investigación CTQ2017-90596-REDT Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-918 Ministerio de Economía y Competitividad SEV-2015-0496 Agencia Estatal de Investigación CEX2019-000917-S European Commission 777222 Agencia Estatal de Investigación PID2020-113058GB-I00 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Published in: | Biomacromolecules, Vol. 23, Issue 7 (June 2022) , p. 2767-2777, ISSN 1526-4602 |
