TY - JOUR
T1 - The internal structure of gadolinium and perfluorocarbon-loaded polymer nanoparticles affects 19F MRI relaxation times
AU - Mali, Alvja
AU - Verbeelen, Margot
AU - White, Paul B.
AU - Staal, Alexander H.J.
AU - van Riessen, N. Koen
AU - Cadiou, Cyril
AU - Chuburu, Françoise
AU - Koshkina, Olga
AU - Srinivas, Mangala
N1 - Funding Information:
This project has received funding from the Horizon 2020 Framework Programme Research and Innovation Programme under the Marie Sklodowska Curie grant agreement No NOVA-MRI (859908). The authors acknowledge the funding from ERC-2014-StG-336454-CoNQUeST, TTW-NWO open technology grant STW-14716, ERC-2015-PoC-713524-CONQUEST, ERC-2019-PoC-862989-CENYA, and ERA-CVD JTC2017-044. The authors kindly thank Bijal K. Bahuleyan (Univ. Rheims), Paul van der Ven (RU), Geert-Jan Janssen (RU) and the General Instruments Department (RU), Peter van Dijk (RU), Daniela Wilson (RU), Eric van Dinther (Radboudumc), Oya Tagit (Radboudumc), Massis Krekorian (Radboudumc), Edyta Swider-Cios (Radboudumc), and Kimberley R. G. Cortenbach (Radboudumc).
Publisher Copyright:
© 2023 The Royal Society of Chemistry.
PY - 2023/10/18
Y1 - 2023/10/18
N2 - 19F magnetic resonance imaging (19F MRI) is an emerging technique for quantitative imaging in novel therapies, such as cellular therapies and theranostic nanocarriers. Nanocarriers loaded with liquid perfluorocarbon (PFC) typically have a (single) core-shell structure with PFC in the core due to the poor miscibility of PFC with organic and inorganic solvents. Paramagnetic relaxation enhancement acts only at a distance of a few angstroms. Thus, efficient modulation of the 19F signal is possible only with fluorophilic PFC-soluble chelates. However, these chelates cannot interact with the surrounding environment and they might result in image artifacts. Conversely, chelates bound to the nanoparticle shell typically have a minimal effect on the 19F signal and a strong impact on the aqueous environment. We show that the confinement of PFC in biodegradable polymeric nanoparticles (NPs) with a multicore structure enables the modulation of longitudinal (T1) and transverse (T2) 19F relaxation, as well as proton (1H) signals, using non-fluorophilic paramagnetic chelates. We compared multicore NPs versus a conventional single core structure, where the PFC is encapsulated in the core(s) and the chelate in the surrounding polymeric matrix. This modulated relaxation also makes multicore NPs sensitive to various acidic pH environments, while preserving their stability. This effect was not observed with single core nanocapsules (NCs). Importantly, paramagnetic chelates affected both T1 and T219F relaxation in multicore NPs, but not in single core NCs. Both relaxation times of the 19F nucleus were enhanced with an increasing concentration of the paramagnetic chelate. Moreover, as the polymeric matrix remained water permeable, proton enhancement additionally was observed in MRI.
AB - 19F magnetic resonance imaging (19F MRI) is an emerging technique for quantitative imaging in novel therapies, such as cellular therapies and theranostic nanocarriers. Nanocarriers loaded with liquid perfluorocarbon (PFC) typically have a (single) core-shell structure with PFC in the core due to the poor miscibility of PFC with organic and inorganic solvents. Paramagnetic relaxation enhancement acts only at a distance of a few angstroms. Thus, efficient modulation of the 19F signal is possible only with fluorophilic PFC-soluble chelates. However, these chelates cannot interact with the surrounding environment and they might result in image artifacts. Conversely, chelates bound to the nanoparticle shell typically have a minimal effect on the 19F signal and a strong impact on the aqueous environment. We show that the confinement of PFC in biodegradable polymeric nanoparticles (NPs) with a multicore structure enables the modulation of longitudinal (T1) and transverse (T2) 19F relaxation, as well as proton (1H) signals, using non-fluorophilic paramagnetic chelates. We compared multicore NPs versus a conventional single core structure, where the PFC is encapsulated in the core(s) and the chelate in the surrounding polymeric matrix. This modulated relaxation also makes multicore NPs sensitive to various acidic pH environments, while preserving their stability. This effect was not observed with single core nanocapsules (NCs). Importantly, paramagnetic chelates affected both T1 and T219F relaxation in multicore NPs, but not in single core NCs. Both relaxation times of the 19F nucleus were enhanced with an increasing concentration of the paramagnetic chelate. Moreover, as the polymeric matrix remained water permeable, proton enhancement additionally was observed in MRI.
UR - http://www.scopus.com/inward/record.url?scp=85176151856&partnerID=8YFLogxK
U2 - 10.1039/d3nr04577c
DO - 10.1039/d3nr04577c
M3 - Article
AN - SCOPUS:85176151856
SN - 2040-3364
VL - 15
SP - 18068
EP - 18079
JO - Nanoscale
JF - Nanoscale
IS - 44
ER -