Aldo Isaac Martínez-Banderas1, Antonio Aires2, Sandra Plaza-García2, Lorena Colás2, Julián A Moreno3, Timothy Ravasi1, Jasmeen S Merzaban1, Pedro Ramos-Cabrer4,5, Aitziber L Cortajarena6,7,8, Jürgen Kosel9. 1. Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Jeddah, 23955-6900, Saudi Arabia. 2. Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 182, 20014, Donostia San Sebastián, Spain. 3. Division of Computer, Electrical and Mathematical Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Jeddah, 23955-6900, Saudi Arabia. 4. Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 182, 20014, Donostia San Sebastián, Spain. pramos@cicbiomagune.es. 5. Ikerbasque, Basque Foundation for Science, Mª Díaz de Haro 3, 48013, Bilbao, Spain. pramos@cicbiomagune.es. 6. Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 182, 20014, Donostia San Sebastián, Spain. alcortajarena@cicbiomagune.es. 7. Ikerbasque, Basque Foundation for Science, Mª Díaz de Haro 3, 48013, Bilbao, Spain. alcortajarena@cicbiomagune.es. 8. IMDEA Nanociencia and Nanobiotechnology Unit Associated to Centro Nacional de Biotecnología (CNB-CSIC), Campus Universitario de Cantoblanco, 28049, Madrid, Spain. alcortajarena@cicbiomagune.es. 9. Division of Computer, Electrical and Mathematical Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Jeddah, 23955-6900, Saudi Arabia. jurgen.kosel@kaust.edu.sa.
Abstract
BACKGROUND: Identifying the precise location of cells and their migration dynamics is of utmost importance for achieving the therapeutic potential of cells after implantation into a host. Magnetic resonance imaging is a suitable, non-invasive technique for cell monitoring when used in combination with contrast agents. RESULTS: This work shows that nanowires with an iron core and an iron oxide shell are excellent materials for this application, due to their customizable magnetic properties and biocompatibility. The longitudinal and transverse magnetic relaxivities of the core-shell nanowires were evaluated at 1.5 T, revealing a high performance as T2 contrast agents. Different levels of oxidation and various surface coatings were tested at 7 T. Their effects on the T2 contrast were reflected in the tailored transverse relaxivities. Finally, the detection of nanowire-labeled breast cancer cells was demonstrated in T2-weighted images of cells implanted in both, in vitro in tissue-mimicking phantoms and in vivo in mouse brain. Labeling the cells with a nanowire concentration of 0.8 μg of Fe/mL allowed the detection of 25 cells/µL in vitro, diminishing the possibility of side effects. This performance enabled an efficient labelling for high-resolution cell detection after in vivo implantation (~ 10 nanowire-labeled cells) over a minimum of 40 days. CONCLUSIONS: Iron-iron oxide core-shell nanowires enabled the efficient and longitudinal cellular detection through magnetic resonance imaging acting as T2 contrast agents. Combined with the possibility of magnetic guidance as well as triggering of cellular responses, for instance by the recently discovered strong photothermal response, opens the door to new horizons in cell therapy and make iron-iron oxide core-shell nanowires a promising theranostic platform.
BACKGROUND: Identifying the precise location of cells and their migration dynamics is of utmost importance for achieving the therapeutic potential of cells after implantation into a host. Magnetic resonance imaging is a suitable, non-invasive technique for cell monitoring when used in combination with contrast agents. RESULTS: This work shows that nanowires with an iron core and an ironoxide shell are excellent materials for this application, due to their customizable magnetic properties and biocompatibility. The longitudinal and transverse magnetic relaxivities of the core-shell nanowires were evaluated at 1.5 T, revealing a high performance as T2 contrast agents. Different levels of oxidation and various surface coatings were tested at 7 T. Their effects on the T2 contrast were reflected in the tailored transverse relaxivities. Finally, the detection of nanowire-labeled breast cancer cells was demonstrated in T2-weighted images of cells implanted in both, in vitro in tissue-mimicking phantoms and in vivo in mouse brain. Labeling the cells with a nanowire concentration of 0.8 μg of Fe/mL allowed the detection of 25 cells/µL in vitro, diminishing the possibility of side effects. This performance enabled an efficient labelling for high-resolution cell detection after in vivo implantation (~ 10 nanowire-labeled cells) over a minimum of 40 days. CONCLUSIONS:Iron-iron oxide core-shell nanowires enabled the efficient and longitudinal cellular detection through magnetic resonance imaging acting as T2 contrast agents. Combined with the possibility of magnetic guidance as well as triggering of cellular responses, for instance by the recently discovered strong photothermal response, opens the door to new horizons in cell therapy and make iron-iron oxide core-shell nanowires a promising theranostic platform.
Authors: Alexsandro Dos Santos E da Cruz; Marcos V Puydinger Dos Santos; Raul B Campanelli; Pascoal G Pagliuso; Jefferson Bettini; Kleber R Pirota; Fanny Béron Journal: Nanoscale Adv Date: 2021-04-19