Cargando…

Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking

[Image: see text] With the advent of novel immunotherapies, interest in ex vivo autologous cell labeling for in vivo cell tracking has revived. However, current clinically available labeling strategies have several drawbacks, such as release of radiolabel over time and cytotoxicity. Poly(lactic-co-g...

Descripción completa

Detalles Bibliográficos
Autores principales: Krekorian, Massis, Sandker, Gerwin G. W., Cortenbach, Kimberley R. G., Tagit, Oya, van Riessen, N. Koen, Raavé, René, Srinivas, Mangala, Figdor, Carl G., Heskamp, Sandra, Aarntzen, Erik H. J. G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377710/
https://www.ncbi.nlm.nih.gov/pubmed/34161070
http://dx.doi.org/10.1021/acs.bioconjchem.1c00271
_version_ 1783740696339939328
author Krekorian, Massis
Sandker, Gerwin G. W.
Cortenbach, Kimberley R. G.
Tagit, Oya
van Riessen, N. Koen
Raavé, René
Srinivas, Mangala
Figdor, Carl G.
Heskamp, Sandra
Aarntzen, Erik H. J. G.
author_facet Krekorian, Massis
Sandker, Gerwin G. W.
Cortenbach, Kimberley R. G.
Tagit, Oya
van Riessen, N. Koen
Raavé, René
Srinivas, Mangala
Figdor, Carl G.
Heskamp, Sandra
Aarntzen, Erik H. J. G.
author_sort Krekorian, Massis
collection PubMed
description [Image: see text] With the advent of novel immunotherapies, interest in ex vivo autologous cell labeling for in vivo cell tracking has revived. However, current clinically available labeling strategies have several drawbacks, such as release of radiolabel over time and cytotoxicity. Poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are clinically used biodegradable carriers of contrast agents, with high loading capacity for multimodal imaging agents. Here we show the development of PLGA-based NPs for ex vivo cell labeling and in vivo cell tracking with SPECT. We used primary amine-modified PLGA polymers (PLGA-NH(2)) to construct NPs similar to unmodified PLGA NPs. PLGA-NH(2) NPs were efficiently radiolabeled without chelator and retained the radionuclide for 2 weeks. Monocyte-derived dendritic cells labeled with [(111)In]In-PLGA-NH(2) showed higher specific activity than those labeled with [(111)In]In-oxine, with no negative effect on cell viability. SPECT/CT imaging showed that radiolabeled THP-1 cells accumulated at the Staphylococcus aureus infection site in mice. In conclusion, PLGA-NH(2) NPs are able to retain (111)In, independent of chelator presence. Furthermore, [(111)In]In-PLGA-NH(2) allows cell labeling with high specific activity and no loss of activity over prolonged time intervals. Finally, in vivo tracking of ex vivo labeled THP-1 cells was demonstrated in an infection model using SPECT/CT imaging.
format Online
Article
Text
id pubmed-8377710
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-83777102021-08-31 Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking Krekorian, Massis Sandker, Gerwin G. W. Cortenbach, Kimberley R. G. Tagit, Oya van Riessen, N. Koen Raavé, René Srinivas, Mangala Figdor, Carl G. Heskamp, Sandra Aarntzen, Erik H. J. G. Bioconjug Chem [Image: see text] With the advent of novel immunotherapies, interest in ex vivo autologous cell labeling for in vivo cell tracking has revived. However, current clinically available labeling strategies have several drawbacks, such as release of radiolabel over time and cytotoxicity. Poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are clinically used biodegradable carriers of contrast agents, with high loading capacity for multimodal imaging agents. Here we show the development of PLGA-based NPs for ex vivo cell labeling and in vivo cell tracking with SPECT. We used primary amine-modified PLGA polymers (PLGA-NH(2)) to construct NPs similar to unmodified PLGA NPs. PLGA-NH(2) NPs were efficiently radiolabeled without chelator and retained the radionuclide for 2 weeks. Monocyte-derived dendritic cells labeled with [(111)In]In-PLGA-NH(2) showed higher specific activity than those labeled with [(111)In]In-oxine, with no negative effect on cell viability. SPECT/CT imaging showed that radiolabeled THP-1 cells accumulated at the Staphylococcus aureus infection site in mice. In conclusion, PLGA-NH(2) NPs are able to retain (111)In, independent of chelator presence. Furthermore, [(111)In]In-PLGA-NH(2) allows cell labeling with high specific activity and no loss of activity over prolonged time intervals. Finally, in vivo tracking of ex vivo labeled THP-1 cells was demonstrated in an infection model using SPECT/CT imaging. American Chemical Society 2021-06-23 2021-08-18 /pmc/articles/PMC8377710/ /pubmed/34161070 http://dx.doi.org/10.1021/acs.bioconjchem.1c00271 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Krekorian, Massis
Sandker, Gerwin G. W.
Cortenbach, Kimberley R. G.
Tagit, Oya
van Riessen, N. Koen
Raavé, René
Srinivas, Mangala
Figdor, Carl G.
Heskamp, Sandra
Aarntzen, Erik H. J. G.
Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking
title Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking
title_full Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking
title_fullStr Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking
title_full_unstemmed Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking
title_short Characterization of Intrinsically Radiolabeled Poly(lactic-co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking
title_sort characterization of intrinsically radiolabeled poly(lactic-co-glycolic acid) nanoparticles for ex vivo autologous cell labeling and in vivo tracking
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377710/
https://www.ncbi.nlm.nih.gov/pubmed/34161070
http://dx.doi.org/10.1021/acs.bioconjchem.1c00271
work_keys_str_mv AT krekorianmassis characterizationofintrinsicallyradiolabeledpolylacticcoglycolicacidnanoparticlesforexvivoautologouscelllabelingandinvivotracking
AT sandkergerwingw characterizationofintrinsicallyradiolabeledpolylacticcoglycolicacidnanoparticlesforexvivoautologouscelllabelingandinvivotracking
AT cortenbachkimberleyrg characterizationofintrinsicallyradiolabeledpolylacticcoglycolicacidnanoparticlesforexvivoautologouscelllabelingandinvivotracking
AT tagitoya characterizationofintrinsicallyradiolabeledpolylacticcoglycolicacidnanoparticlesforexvivoautologouscelllabelingandinvivotracking
AT vanriessennkoen characterizationofintrinsicallyradiolabeledpolylacticcoglycolicacidnanoparticlesforexvivoautologouscelllabelingandinvivotracking
AT raaverene characterizationofintrinsicallyradiolabeledpolylacticcoglycolicacidnanoparticlesforexvivoautologouscelllabelingandinvivotracking
AT srinivasmangala characterizationofintrinsicallyradiolabeledpolylacticcoglycolicacidnanoparticlesforexvivoautologouscelllabelingandinvivotracking
AT figdorcarlg characterizationofintrinsicallyradiolabeledpolylacticcoglycolicacidnanoparticlesforexvivoautologouscelllabelingandinvivotracking
AT heskampsandra characterizationofintrinsicallyradiolabeledpolylacticcoglycolicacidnanoparticlesforexvivoautologouscelllabelingandinvivotracking
AT aarntzenerikhjg characterizationofintrinsicallyradiolabeledpolylacticcoglycolicacidnanoparticlesforexvivoautologouscelllabelingandinvivotracking