RT Journal Article
T1 Dual-labeled nanoparticles based on small extracellular vesicles for tumor detection
A1 Santos Coquillat, Ana
A1 Herreros Pérez, Desiré
A1 Samaniego, Rafael
A1 González, María Isabel
A1 Cusso Mula, Lorena
A1 Desco Menéndez, Manuel
A1 Salinas Rodríguez, Beatriz
AB Background: Small extracellular vesicles (sEVs) are emerging natural nanoplatforms in cancer diagnosis and therapy, through the incorporation of signal components or drugs in their structure. However, for their translation into the clinical field, there is still a lack of tools that enable a deeper understanding of their in vivo pharmacokinetics or their interactions with the cells of the tumor microenvironment. In this study, we have designed a dual-sEV probe based on radioactive and fluorescent labeling of goat milk sEVs. Results: The imaging nanoprobe was tested in vitro and in vivo in a model of glioblastoma. In vitro assessment of the uptake of the dual probe in different cell populations (RAW 264.7, U87, and HeLa) by optical and nuclear techniques (gamma counter, confocal imaging, and flow cytometry) revealed the highest uptake in inflammatory cells (RAW 264.7), followed by glioblastoma U87 cells. In vivo evaluation of the pharmacokinetic properties of nanoparticles confirmed a blood circulation time of ~ 8 h and primarily hepatobiliary elimination. The diagnostic capability of the dual nanoprobe was confirmed in vivo in a glioblastoma xenograft model, which showed intense in vivo uptake of the SEV-based probe in tumor tissue. Histological assessment by confocal imaging enabled quantification of tumor populations and confirmed uptake in tumor cells and tumor-associated macrophages, followed by cancer-associated fibroblasts and endothelial cells. Conclusions: We have developed a chemical approach for dual radioactive and fluorescent labeling of sEVs. This methodology enables in vivo and in vitro study of these vesicles after exogenous administration. The dual nanoprobe would be a promising technology for cancer diagnosis and a powerful tool for studying the biological behavior of these nanosystems for use in drug delivery.
PB BMC
SN 1745-6150
YR 2022
FD 2022-11-14
LK https://hdl.handle.net/10016/37192
UL https://hdl.handle.net/10016/37192
LA eng
NO This study was supported by Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III, project "PI20/01632" and "PT20/00044", co-funded by the European Regional Development Fund (ERDF), "A way of making Europe", by Comunidad de Madrid, project "Y2018/NMT-4949 (NanoLiver-CM)" and "S2017/BMD-3867 (RENIM-CM)", co-funded by the European Structural and Investment Fund, and by Agencia Estatal de Investigación "PID2019-110369RB-I00/AEI/https://doi.org/10.13039/501100011033" grant. This work was also supported by "Diagnosis and treatment follow-up of severe Staphylococcal infections with anti-Staphylococcal antibodies and immune-PET - Grant Fundación BBVA a Equipos de Investigación Científica 2018 and Ramon Areces Grant "Imagen molecular de la infección por Clostridiodes difficile". Grant EQC2019-006674-P funded by MCIN/AEI https://doi.org/10.13039/501100011033 and by "ERDF A way of making Europe". A. Santos-Coquillat is grateful for fnancial support from Consejería de Educación e Investigación Comunidad de Madrid, co-fnanced by European Social Fund (ESF) grant PEJD-2018-POST/BMD-9592 and the Sara Borrell Fellowship from Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III grant CD19/00136. M.I. González is funded by Instituto de Investigación Sanitaria Gregorio Marañón, Intramural Programme for the Promotion of R&D&I 2021, Sub-programme "Predoctoral training contract".
DS e-Archivo
RD 27 jul. 2024