Iron-based compounds coordinated with phospho-polymers as biocompatible probes for dual 31P/1H magnetic resonance imaging and spectroscopy
Language English Country Great Britain, England Media electronic
Document type Journal Article
Grant support
271723
Grantová Agentura, Univerzita Karlova
NU20-08-00095
Ministerstvo Zdravotnictví Ceské Republiky
Programme EXCELES
National Institute for Research of Metabolic and Cardiovascular Diseases
LX22NPO5104
National Institute for Research of Metabolic and Cardiovascular Diseases
PubMed
38360883
PubMed Central
PMC10869799
DOI
10.1038/s41598-024-54158-x
PII: 10.1038/s41598-024-54158-x
Knihovny.cz E-resources
- MeSH
- Magnetic Resonance Spectroscopy MeSH
- Magnetic Resonance Imaging * methods MeSH
- Polymers * MeSH
- Tissue Distribution MeSH
- Water MeSH
- Iron MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Polymers * MeSH
- Water MeSH
- Iron MeSH
In this work, we present the synthesis and evaluation of magnetic resonance (MR) properties of novel phosphorus/iron-containing probes for dual 31P and 1H MR imaging and spectroscopy (MRI and MRS). The presented probes are composed of biocompatible semitelechelic and multivalent phospho-polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) coordinated with small paramagnetic Fe3+ ions or superparamagnetic maghemite (γ-Fe2O3) nanoparticles via deferoxamine group linked to the end or along the polymer chains. All probes provided very short 1H T1 and T2 relaxation times even at low iron concentrations. The presence of iron had a significant impact on the shortening of 31P relaxation, with the effect being more pronounced for probes based on γ-Fe2O3 and multivalent polymer. While the water-soluble probe having one Fe3+ ion per polymer chain was satisfactorily visualized by both 31P-MRS and 31P-MRI, the probe with multiple Fe3+ ions could only be detected by 31P-MRS, and the probes consisting of γ-Fe2O3 nanoparticles could not be imaged by either technique due to their ultra-short 31P relaxations. In this proof-of-principle study performed on phantoms at a clinically relevant magnetic fields, we demonstrated how the different forms and concentrations of iron affect both the 1H MR signal of the surrounding water molecules and the 31P MR signal of the phospho-polymer probe. Thus, this double contrast can be exploited to simultaneously visualize body anatomy and monitor probe biodistribution.
See more in PubMed
Jirák D, Vítek F. Basics of Medical Physics. Karolinum Press; 2017.
Wahsner J, Gale EM, Rodriguez-Rodriguez A, Caravan P. Chemistry of MRI contrast agents: Current challenges and new frontiers. Chem. Rev. 2019;119:957–1057. doi: 10.1021/acs.chemrev.8b00363. PubMed DOI PMC
Fatima A, et al. Recent advances in gadolinium based contrast agents for bioimaging applications. Nanomaterials (Basel) 2021 doi: 10.3390/nano11092449. PubMed DOI PMC
Rogosnitzky M, Branch S. Gadolinium-based contrast agent toxicity: A review of known and proposed mechanisms. Biometals. 2016;29:365–376. doi: 10.1007/s10534-016-9931-7. PubMed DOI PMC
Dulinska-Litewka J, et al. Superparamagnetic iron oxide nanoparticles-current and prospective medical applications. Materials (Basel) 2019 doi: 10.3390/ma12040617. PubMed DOI PMC
Saudek F, et al. Magnetic resonance imaging of pancreatic islets transplanted into the liver in humans. Transplantation. 2010;90:1602–1606. doi: 10.1097/TP.0b013e3181ffba5e. PubMed DOI
Patil S, Jirák D, Saudek F, Hájek M, Scheffler K. Positive contrast visualization of SPIO-labeled pancreatic islets using echo-dephased steady-state free precession. Eur. Radiol. 2011;21:214–220. doi: 10.1007/s00330-010-1909-1. PubMed DOI
Deligianni X, et al. In vivo visualization of cells labeled with superparamagnetic iron oxides by a sub-millisecond gradient echo sequence. Magn. Reson. Mater. Phys. 2014;27:329–337. doi: 10.1007/s10334-013-0422-3. PubMed DOI
Babic M, et al. Poly(L-lysine)-modified iron oxide nanoparticles for stem cell labeling. Bioconjug. Chem. 2008;19:740–750. doi: 10.1021/bc700410z. PubMed DOI
Wang R, et al. A class of water-soluble Fe(iii) coordination complexes as T1-weighted MRI contrast agents. J. Mater. Chem. B. 2021;9:1787–1791. doi: 10.1039/d0tb02716b. PubMed DOI
Palagi L, et al. Fe(deferasirox): An Iron(III)-based magnetic resonance imaging T1 contrast agent endowed with remarkable molecular and functional characteristics. J. Am. Chem. Soc. 2021;143:14178–14188. doi: 10.1021/jacs.1c04963. PubMed DOI
Marasini R, Rayamajhi S, Moreno-Sanchez A, Aryal S. Iron(iii) chelated paramagnetic polymeric nanoparticle formulation as a next-generation T1-weighted MRI contrast agent. RSC Adv. 2021;11:32216–32226. doi: 10.1039/d1ra05544e. PubMed DOI PMC
Hu R, et al. X-nuclei imaging: Current state, technical challenges, and future directions. J. Magn. Reson. Imaging. 2020;51:355–376. doi: 10.1002/jmri.26780. PubMed DOI
Liu YC, Gu YN, Yu X. Assessing tissue metabolism by phosphorous-31 magnetic resonance spectroscopy and imaging: A methodology review. Quant. Imaging Med. Surg. 2017;7:707–726. doi: 10.21037/qims.2017.11.03. PubMed DOI PMC
Neeman M, Rushkin E, Kaye AM, Degani H. 31P-NMR studies of phosphate transfer rates in T47D human breast cancer cells. Biochim. Biophys. Acta. 1987;930:179–192. doi: 10.1016/0167-4889(87)90030-9. PubMed DOI
Levine SR, et al. Human focal cerebral ischemia: Evaluation of brain pH and energy metabolism with P-31 NMR spectroscopy. Radiology. 1992;185:537–544. doi: 10.1148/radiology.185.2.1410369. PubMed DOI
Kracikova L, et al. Phosphorus-containing polymers as sensitive biocompatible probes for (31)P magnetic resonance. Molecules. 2023 doi: 10.3390/molecules28052334. PubMed DOI PMC
Kracikova L, et al. Phosphorus-containing polymeric Zwitterion: A pioneering bioresponsive probe for (31) P-magnetic resonance imaging. Macromol. Biosci. 2022;22:e2100523. doi: 10.1002/mabi.202100523. PubMed DOI
Ziolkowska N, Vit M, Laga R, Jirak D. Iron-doped calcium phytate nanoparticles as a bio-responsive contrast agent in (1)H/(31)P magnetic resonance imaging. Sci. Rep. 2022;12:2118. doi: 10.1038/s41598-022-06125-7. PubMed DOI PMC
Pechrova Z, Lobaz V, Konefał M, Konefał R, Hruby M. Colloidal probe based on iron(III)-doped calcium phytate nanoparticles for 31P NMR monitoring of bacterial siderophores. Colloid Interface Sci. Commun. 2021;42:100427. doi: 10.1016/j.colcom.2021.100427. DOI
Andrianov AK. Water-soluble polyphosphazenes for biomedical applications. J. Inorg. Organomet. Polym. Mater. 2006;16:397–406. doi: 10.1007/s10904-006-9065-4. DOI
Pelosi C, Tinè MR, Wurm FR. Main-chain water-soluble polyphosphoesters: Multi-functional polymers as degradable PEG-alternatives for biomedical applications. Eur. Polym. J. 2020 doi: 10.1016/j.eurpolymj.2020.110079. DOI
Kojima C, et al. Different antifouling effects of random and block copolymers comprising 2-methacryloyloxyethyl phosphorylcholine and dodecyl methacrylate. Eur. Polym. J. 2020 doi: 10.1016/j.eurpolymj.2020.109932. DOI
Goda T, Ishihara K, Miyahara Y. Critical update on 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer science. J. Appl. Polym. Sci. 2015 doi: 10.1002/app.41766. DOI
Subr V, Ulbrich K. Synthesis and properties of new N-(2-hydroxypropyl)-methacrylamide copolymers containing thiazolidine-2-thione reactive groups. React. Funct. Polym. 2006;66:1525–1538. doi: 10.1016/j.reactfunctpolym.2006.05.002. DOI
Subr V, Kostka L, Strohalm J, Etrych T, Ulbrich K. Synthesis of Well-Defined Semitelechelic Poly[N-(2-hydroxypropyl)methacrylamide] Polymers with Functional Group at the α-End of the Polymer Chain by RAFT Polymerization. Macromolecules. 2013;46:2100–2108. doi: 10.1021/ma400042u. DOI
Kracíková L, et al. Polymer-colloidal systems as MRI-detectable nanocarriers for peptide vaccine delivery. Eur. Polym. J. 2022 doi: 10.1016/j.eurpolymj.2022.111704. DOI
Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. J. Control Release. 2000;65:271–284. doi: 10.1016/s0168-3659(99)00248-5. PubMed DOI
Schupp T, Waldmeier U, Divers M. Biosynthesis of desferrioxamine-B in Streptomyces-Pilosus—Evidence for the involvement of lysine decarboxylase. Fems Microbiol. Lett. 1987;42:135–139. doi: 10.1111/j.1574-6968.1987.tb02060.x. DOI
Evers A, Hancock RD, Martell AE, Motekaitis RJ. Metal ion recognition in ligands with negatively charged oxygen donor groups. Complexation of iron(III), gallium(III), indium(III), aluminum(III), and other highly charged metal ions. Inorg. Chem. 1989;28:2189–2195. doi: 10.1021/ic00310a035. DOI
Aaseth, J., Crisponi, G. & Andersen, O. Chelation Therapy in the Treatment of Metal Intoxication. Chelation Therapy in the Treatment of Metal Intoxication, 1–371. 10.1016/C2014-0-01302-0 (2016).
Vangijzegem T, et al. Superparamagnetic iron oxide nanoparticles (SPION): From fundamentals to state-of-the-art innovative applications for cancer therapy. Pharmaceutics. 2023 doi: 10.3390/pharmaceutics15010236. PubMed DOI PMC
Babic M, et al. Poly(N, N-dimethylacrylamide)-coated maghemite nanoparticles for stem cell labeling. Bioconjug. Chem. 2009;20:283–294. doi: 10.1021/bc800373x. PubMed DOI
Laurent S, et al. Magnetic iron oxide nanoparticles: Synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev. 2008;108:2064–2110. doi: 10.1021/cr068445e. PubMed DOI
Pollert E, et al. Magnetic poly(glycidyl methacrylate) microspheres containing maghemite prepared by emulsion polymerization. J. Magn. Magn. Mater. 2006;306:241–247. doi: 10.1016/j.jmmm.2006.03.069. DOI
Reimer P, Balzer T. Ferucarbotran (Resovist): A new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: Properties, clinical development, and applications. Eur. Radiol. 2003;13:1266–1276. doi: 10.1007/s00330-002-1721-7. PubMed DOI
Alzola-Aldamizetxebarria S, Fernandez-Mendez L, Padro D, Ruiz-Cabello J, Ramos-Cabrer P. A comprehensive introduction to magnetic resonance imaging relaxometry and contrast agents. ACS Omega. 2022;7:36905–36917. doi: 10.1021/acsomega.2c03549. PubMed DOI PMC
Huh YM, et al. In vivo magnetic resonance detection of cancer by using multifunctional magnetic nanocrystals. J. Am. Chem. Soc. 2005;127:12387–12391. doi: 10.1021/ja052337c. PubMed DOI
Gossuin Y, Gillis P, Hocq A, Vuong QL, Roch A. Magnetic resonance relaxation properties of superparamagnetic particles. Wires Nanomed. Nanobiotechnol. 2009;1:299–310. doi: 10.1002/wnan.36. PubMed DOI