Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles

Autores
Demichelis, Maria Paola; Sommi, Patrizia; Romanini, Nicola; Portu, Agustina Mariana; Gadan, Mario Alberto; Bortolussi, Silva; Postuma, Ian; Casu, Alberto; Falqui, Andrea; Palamà, Maria Elisabetta Federica; Scaglione, Silvia; Tauceri, Francesca; Paganelli, Giovanni; Tazzari, Marcella; Anselmi Tamburini, Umberto
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Nanomedicine offers promising strategies for targeted drug delivery, imaging, and molecular-level therapies. However, the clinical translation of nanomedicine has often been hindered by the complex interactions of nanoparticles (NPs) with biological systems. This study investigates a cell-based delivery platform designed to overcome some of these limitations, using clinical-grade tumor-infiltrating lymphocytes (TILs) as biological carriers of boron carbide (B4C) NPs in boron neutron capture therapy (BNCT). Biological vectors, such as TILs, could enable selective tumor targeting, leading to highly localized 10B levels and minimizing off-target accumulation. We evaluated the uptake and retention of composite Fe2O3–B4C NPs (FeBNPs) using both immortalized Jurkat T cells and primary human TILs. Both cell types efficiently internalized FeBNPs without cytotoxic effects, maintained their functionalities, and retained the boron-rich NPs for up to 72 h. Imaging confirmed intracellular localization, and neutron autoradiography demonstrated that TILs accumulated sufficient 10B for therapeutic efficacy, eliminating the need for isotopically enriched compounds like L-4-boronophenylalanine (BPA) or sodium borocaptate (BSH). Coculture experiments with Jurkat and HeLa cells confirmed that lymphocyte-delivered boron could mediate localized radiation damage via neutron capture. These findings support the concept of TILs as “Trojan Horses” for boron delivery, allowing for overcoming traditional barriers in NP-based therapies and taking advantage of their innate tumor-homing ability. This approach not only enhances BNCT selectivity and efficacy but also supports the integration of nanomedicine with adoptive cell therapy in a combined cancer treatment framework.
Fil: Demichelis, Maria Paola. Universita degli Studi di Pavia; Italia
Fil: Sommi, Patrizia. Universita degli Studi di Pavia; Italia
Fil: Romanini, Nicola. Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”; Italia
Fil: Portu, Agustina Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: Gadan, Mario Alberto. Comisión Nacional de Energía Atómica; Argentina
Fil: Bortolussi, Silva. Universita degli Studi di Pavia; Italia. Istituto Nazionale di Fisica Nucleare; Italia
Fil: Postuma, Ian. Istituto Nazionale di Fisica Nucleare; Italia
Fil: Casu, Alberto. Università degli Studi di Milano; Italia
Fil: Falqui, Andrea. Università degli Studi di Milano; Italia
Fil: Palamà, Maria Elisabetta Federica. Università degli Studi di Milano; Italia
Fil: Scaglione, Silvia. Consiglio Nazionale delle Ricerche; Italia
Fil: Tauceri, Francesca. Morgagni-Pierantoni Hospital; Italia
Fil: Paganelli, Giovanni. Istituto Romagnolo per lo Studio dei Tumori; Italia. Universita degli Studi di Pavia; Italia
Fil: Tazzari, Marcella. Istituto Romagnolo per lo Studio dei Tumori; Italia
Fil: Anselmi Tamburini, Umberto. Università di Ferrara; Italia. Istituto Nazionale di Fisica Nucleare; Italia
Materia
Nanoparticles
Adoptive cell therapy
Boron carbide
BNCT
Tumor-infiltrating lymphocytes
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/281504
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/281504
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide NanoparticlesDemichelis, Maria PaolaSommi, PatriziaRomanini, NicolaPortu, Agustina MarianaGadan, Mario AlbertoBortolussi, SilvaPostuma, IanCasu, AlbertoFalqui, AndreaPalamà, Maria Elisabetta FedericaScaglione, SilviaTauceri, FrancescaPaganelli, GiovanniTazzari, MarcellaAnselmi Tamburini, UmbertoNanoparticlesAdoptive cell therapyBoron carbideBNCTTumor-infiltrating lymphocyteshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Nanomedicine offers promising strategies for targeted drug delivery, imaging, and molecular-level therapies. However, the clinical translation of nanomedicine has often been hindered by the complex interactions of nanoparticles (NPs) with biological systems. This study investigates a cell-based delivery platform designed to overcome some of these limitations, using clinical-grade tumor-infiltrating lymphocytes (TILs) as biological carriers of boron carbide (B4C) NPs in boron neutron capture therapy (BNCT). Biological vectors, such as TILs, could enable selective tumor targeting, leading to highly localized 10B levels and minimizing off-target accumulation. We evaluated the uptake and retention of composite Fe2O3–B4C NPs (FeBNPs) using both immortalized Jurkat T cells and primary human TILs. Both cell types efficiently internalized FeBNPs without cytotoxic effects, maintained their functionalities, and retained the boron-rich NPs for up to 72 h. Imaging confirmed intracellular localization, and neutron autoradiography demonstrated that TILs accumulated sufficient 10B for therapeutic efficacy, eliminating the need for isotopically enriched compounds like L-4-boronophenylalanine (BPA) or sodium borocaptate (BSH). Coculture experiments with Jurkat and HeLa cells confirmed that lymphocyte-delivered boron could mediate localized radiation damage via neutron capture. These findings support the concept of TILs as “Trojan Horses” for boron delivery, allowing for overcoming traditional barriers in NP-based therapies and taking advantage of their innate tumor-homing ability. This approach not only enhances BNCT selectivity and efficacy but also supports the integration of nanomedicine with adoptive cell therapy in a combined cancer treatment framework.Fil: Demichelis, Maria Paola. Universita degli Studi di Pavia; ItaliaFil: Sommi, Patrizia. Universita degli Studi di Pavia; ItaliaFil: Romanini, Nicola. Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”; ItaliaFil: Portu, Agustina Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Gadan, Mario Alberto. Comisión Nacional de Energía Atómica; ArgentinaFil: Bortolussi, Silva. Universita degli Studi di Pavia; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Postuma, Ian. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Casu, Alberto. Università degli Studi di Milano; ItaliaFil: Falqui, Andrea. Università degli Studi di Milano; ItaliaFil: Palamà, Maria Elisabetta Federica. Università degli Studi di Milano; ItaliaFil: Scaglione, Silvia. Consiglio Nazionale delle Ricerche; ItaliaFil: Tauceri, Francesca. Morgagni-Pierantoni Hospital; ItaliaFil: Paganelli, Giovanni. Istituto Romagnolo per lo Studio dei Tumori; Italia. Universita degli Studi di Pavia; ItaliaFil: Tazzari, Marcella. Istituto Romagnolo per lo Studio dei Tumori; ItaliaFil: Anselmi Tamburini, Umberto. Università di Ferrara; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaAmerican Chemical Society2025-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/281504Demichelis, Maria Paola; Sommi, Patrizia; Romanini, Nicola; Portu, Agustina Mariana; Gadan, Mario Alberto; et al.; Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles; American Chemical Society; ACS Nano; 19; 50; 12-2025; 42158-421741936-0851CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acsnano.5c12640info:eu-repo/semantics/altIdentifier/doi/10.1021/acsnano.5c12640info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-26T09:58:23Zoai:ri.conicet.gov.ar:11336/281504instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-02-26 09:58:23.975CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles
title Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles
spellingShingle Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles
Demichelis, Maria Paola
Nanoparticles
Adoptive cell therapy
Boron carbide
BNCT
Tumor-infiltrating lymphocytes
title_short Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles
title_full Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles
title_fullStr Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles
title_full_unstemmed Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles
title_sort Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles
dc.creator.none.fl_str_mv Demichelis, Maria Paola
Sommi, Patrizia
Romanini, Nicola
Portu, Agustina Mariana
Gadan, Mario Alberto
Bortolussi, Silva
Postuma, Ian
Casu, Alberto
Falqui, Andrea
Palamà, Maria Elisabetta Federica
Scaglione, Silvia
Tauceri, Francesca
Paganelli, Giovanni
Tazzari, Marcella
Anselmi Tamburini, Umberto
author Demichelis, Maria Paola
author_facet Demichelis, Maria Paola
Sommi, Patrizia
Romanini, Nicola
Portu, Agustina Mariana
Gadan, Mario Alberto
Bortolussi, Silva
Postuma, Ian
Casu, Alberto
Falqui, Andrea
Palamà, Maria Elisabetta Federica
Scaglione, Silvia
Tauceri, Francesca
Paganelli, Giovanni
Tazzari, Marcella
Anselmi Tamburini, Umberto
author_role author
author2 Sommi, Patrizia
Romanini, Nicola
Portu, Agustina Mariana
Gadan, Mario Alberto
Bortolussi, Silva
Postuma, Ian
Casu, Alberto
Falqui, Andrea
Palamà, Maria Elisabetta Federica
Scaglione, Silvia
Tauceri, Francesca
Paganelli, Giovanni
Tazzari, Marcella
Anselmi Tamburini, Umberto
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Nanoparticles
Adoptive cell therapy
Boron carbide
BNCT
Tumor-infiltrating lymphocytes
topic Nanoparticles
Adoptive cell therapy
Boron carbide
BNCT
Tumor-infiltrating lymphocytes
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Nanomedicine offers promising strategies for targeted drug delivery, imaging, and molecular-level therapies. However, the clinical translation of nanomedicine has often been hindered by the complex interactions of nanoparticles (NPs) with biological systems. This study investigates a cell-based delivery platform designed to overcome some of these limitations, using clinical-grade tumor-infiltrating lymphocytes (TILs) as biological carriers of boron carbide (B4C) NPs in boron neutron capture therapy (BNCT). Biological vectors, such as TILs, could enable selective tumor targeting, leading to highly localized 10B levels and minimizing off-target accumulation. We evaluated the uptake and retention of composite Fe2O3–B4C NPs (FeBNPs) using both immortalized Jurkat T cells and primary human TILs. Both cell types efficiently internalized FeBNPs without cytotoxic effects, maintained their functionalities, and retained the boron-rich NPs for up to 72 h. Imaging confirmed intracellular localization, and neutron autoradiography demonstrated that TILs accumulated sufficient 10B for therapeutic efficacy, eliminating the need for isotopically enriched compounds like L-4-boronophenylalanine (BPA) or sodium borocaptate (BSH). Coculture experiments with Jurkat and HeLa cells confirmed that lymphocyte-delivered boron could mediate localized radiation damage via neutron capture. These findings support the concept of TILs as “Trojan Horses” for boron delivery, allowing for overcoming traditional barriers in NP-based therapies and taking advantage of their innate tumor-homing ability. This approach not only enhances BNCT selectivity and efficacy but also supports the integration of nanomedicine with adoptive cell therapy in a combined cancer treatment framework.
Fil: Demichelis, Maria Paola. Universita degli Studi di Pavia; Italia
Fil: Sommi, Patrizia. Universita degli Studi di Pavia; Italia
Fil: Romanini, Nicola. Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”; Italia
Fil: Portu, Agustina Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Comisión Nacional de Energía Atómica; Argentina
Fil: Gadan, Mario Alberto. Comisión Nacional de Energía Atómica; Argentina
Fil: Bortolussi, Silva. Universita degli Studi di Pavia; Italia. Istituto Nazionale di Fisica Nucleare; Italia
Fil: Postuma, Ian. Istituto Nazionale di Fisica Nucleare; Italia
Fil: Casu, Alberto. Università degli Studi di Milano; Italia
Fil: Falqui, Andrea. Università degli Studi di Milano; Italia
Fil: Palamà, Maria Elisabetta Federica. Università degli Studi di Milano; Italia
Fil: Scaglione, Silvia. Consiglio Nazionale delle Ricerche; Italia
Fil: Tauceri, Francesca. Morgagni-Pierantoni Hospital; Italia
Fil: Paganelli, Giovanni. Istituto Romagnolo per lo Studio dei Tumori; Italia. Universita degli Studi di Pavia; Italia
Fil: Tazzari, Marcella. Istituto Romagnolo per lo Studio dei Tumori; Italia
Fil: Anselmi Tamburini, Umberto. Università di Ferrara; Italia. Istituto Nazionale di Fisica Nucleare; Italia
description Nanomedicine offers promising strategies for targeted drug delivery, imaging, and molecular-level therapies. However, the clinical translation of nanomedicine has often been hindered by the complex interactions of nanoparticles (NPs) with biological systems. This study investigates a cell-based delivery platform designed to overcome some of these limitations, using clinical-grade tumor-infiltrating lymphocytes (TILs) as biological carriers of boron carbide (B4C) NPs in boron neutron capture therapy (BNCT). Biological vectors, such as TILs, could enable selective tumor targeting, leading to highly localized 10B levels and minimizing off-target accumulation. We evaluated the uptake and retention of composite Fe2O3–B4C NPs (FeBNPs) using both immortalized Jurkat T cells and primary human TILs. Both cell types efficiently internalized FeBNPs without cytotoxic effects, maintained their functionalities, and retained the boron-rich NPs for up to 72 h. Imaging confirmed intracellular localization, and neutron autoradiography demonstrated that TILs accumulated sufficient 10B for therapeutic efficacy, eliminating the need for isotopically enriched compounds like L-4-boronophenylalanine (BPA) or sodium borocaptate (BSH). Coculture experiments with Jurkat and HeLa cells confirmed that lymphocyte-delivered boron could mediate localized radiation damage via neutron capture. These findings support the concept of TILs as “Trojan Horses” for boron delivery, allowing for overcoming traditional barriers in NP-based therapies and taking advantage of their innate tumor-homing ability. This approach not only enhances BNCT selectivity and efficacy but also supports the integration of nanomedicine with adoptive cell therapy in a combined cancer treatment framework.
publishDate 2025
dc.date.none.fl_str_mv 2025-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/281504
Demichelis, Maria Paola; Sommi, Patrizia; Romanini, Nicola; Portu, Agustina Mariana; Gadan, Mario Alberto; et al.; Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles; American Chemical Society; ACS Nano; 19; 50; 12-2025; 42158-42174
1936-0851
CONICET Digital
CONICET
url http://hdl.handle.net/11336/281504
identifier_str_mv Demichelis, Maria Paola; Sommi, Patrizia; Romanini, Nicola; Portu, Agustina Mariana; Gadan, Mario Alberto; et al.; Coupling Adoptive Cell Therapy with Boron Neutron Capture Therapy: Using Functional Tumor-Infiltrating Lymphocytes for Tumor Delivery of Boron Carbide Nanoparticles; American Chemical Society; ACS Nano; 19; 50; 12-2025; 42158-42174
1936-0851
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acsnano.5c12640
info:eu-repo/semantics/altIdentifier/doi/10.1021/acsnano.5c12640
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.176822

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