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Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer

Aminobisphosphonates, such as zoledronic acid (ZA), have shown potential in the treatment of different malignancies, including colorectal carcinoma (CRC). Yet, their clinical exploitation is limited by their high bone affinity and modest bioavailability. Here, ZA is encapsulated into the aqueous cor...

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Autores principales: Di Mascolo, Daniele, Varesano, Serena, Benelli, Roberto, Mollica, Hilaria, Salis, Annalisa, Zocchi, Maria Raffaella, Decuzzi, Paolo, Poggi, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017311/
https://www.ncbi.nlm.nih.gov/pubmed/31906080
http://dx.doi.org/10.3390/cancers12010104
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author Di Mascolo, Daniele
Varesano, Serena
Benelli, Roberto
Mollica, Hilaria
Salis, Annalisa
Zocchi, Maria Raffaella
Decuzzi, Paolo
Poggi, Alessandro
author_facet Di Mascolo, Daniele
Varesano, Serena
Benelli, Roberto
Mollica, Hilaria
Salis, Annalisa
Zocchi, Maria Raffaella
Decuzzi, Paolo
Poggi, Alessandro
author_sort Di Mascolo, Daniele
collection PubMed
description Aminobisphosphonates, such as zoledronic acid (ZA), have shown potential in the treatment of different malignancies, including colorectal carcinoma (CRC). Yet, their clinical exploitation is limited by their high bone affinity and modest bioavailability. Here, ZA is encapsulated into the aqueous core of spherical polymeric nanoparticles (SPNs), whose size and architecture resemble that of biological vesicles. On Vδ2 T cells, derived from the peripheral blood of healthy donors and CRC patients, ZA-SPNs induce proliferation and trigger activation up to three orders of magnitude more efficiently than soluble ZA. These activated Vδ2 T cells kill CRC cells and tumor spheroids, and are able to migrate toward CRC cells in a microfluidic system. Notably, ZA-SPNs can also stimulate the proliferation of Vδ2 T cells from the tumor-infiltrating lymphocytes of CRC patients and boost their cytotoxic activity against patients’ autologous tumor organoids. These data represent a first step toward the use of nanoformulated ZA for immunotherapy in CRC patients.
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spelling pubmed-70173112020-02-28 Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer Di Mascolo, Daniele Varesano, Serena Benelli, Roberto Mollica, Hilaria Salis, Annalisa Zocchi, Maria Raffaella Decuzzi, Paolo Poggi, Alessandro Cancers (Basel) Article Aminobisphosphonates, such as zoledronic acid (ZA), have shown potential in the treatment of different malignancies, including colorectal carcinoma (CRC). Yet, their clinical exploitation is limited by their high bone affinity and modest bioavailability. Here, ZA is encapsulated into the aqueous core of spherical polymeric nanoparticles (SPNs), whose size and architecture resemble that of biological vesicles. On Vδ2 T cells, derived from the peripheral blood of healthy donors and CRC patients, ZA-SPNs induce proliferation and trigger activation up to three orders of magnitude more efficiently than soluble ZA. These activated Vδ2 T cells kill CRC cells and tumor spheroids, and are able to migrate toward CRC cells in a microfluidic system. Notably, ZA-SPNs can also stimulate the proliferation of Vδ2 T cells from the tumor-infiltrating lymphocytes of CRC patients and boost their cytotoxic activity against patients’ autologous tumor organoids. These data represent a first step toward the use of nanoformulated ZA for immunotherapy in CRC patients. MDPI 2019-12-31 /pmc/articles/PMC7017311/ /pubmed/31906080 http://dx.doi.org/10.3390/cancers12010104 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Di Mascolo, Daniele
Varesano, Serena
Benelli, Roberto
Mollica, Hilaria
Salis, Annalisa
Zocchi, Maria Raffaella
Decuzzi, Paolo
Poggi, Alessandro
Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer
title Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer
title_full Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer
title_fullStr Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer
title_full_unstemmed Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer
title_short Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer
title_sort nanoformulated zoledronic acid boosts the vδ2 t cell immunotherapeutic potential in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017311/
https://www.ncbi.nlm.nih.gov/pubmed/31906080
http://dx.doi.org/10.3390/cancers12010104
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