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Volume 12
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10.3390/cancers12010104
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Article

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

by
Daniele Di Mascolo
1,†,
Serena Varesano
2,†,
Roberto Benelli
3,
Hilaria Mollica
1,
Annalisa Salis
4,
Maria Raffaella Zocchi
5,
Paolo Decuzzi
1,‡ and
Alessandro Poggi
2,*,‡
1
Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia, 16163 Genoa, Italy
2
Molecular Oncology and Angiogenesis Unit, IRCCS Policlinico San Martino, 16132 Genoa, Italy
3
Immunology Unit, Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
4
CEBR, University of Genoa, 16132 Genoa, Italy
5
Division of Immunology, Transplants and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
P.D. and A.P. share the senior authorship.
Cancers 2020, 12(1), 104; https://doi.org/10.3390/cancers12010104
Submission received: 20 November 2019 / Revised: 19 December 2019 / Accepted: 29 December 2019 / Published: 31 December 2019
(This article belongs to the Special Issue Cancer Nanomedicine)
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Abstract

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.
Keywords: Vδ2 T cells; zoledronic acid; polymeric nanoconstruct; anti-tumor immunity; colorectal carcinoma Vδ2 T cells; zoledronic acid; polymeric nanoconstruct; anti-tumor immunity; colorectal carcinoma

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MDPI and ACS Style

Di Mascolo, D.; Varesano, S.; Benelli, R.; Mollica, H.; Salis, A.; Zocchi, M.R.; Decuzzi, P.; Poggi, A. Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer. Cancers 2020, 12, 104. https://doi.org/10.3390/cancers12010104

AMA Style

Di Mascolo D, Varesano S, Benelli R, Mollica H, Salis A, Zocchi MR, Decuzzi P, Poggi A. Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer. Cancers. 2020; 12(1):104. https://doi.org/10.3390/cancers12010104

Chicago/Turabian Style

Di Mascolo, Daniele, Serena Varesano, Roberto Benelli, Hilaria Mollica, Annalisa Salis, Maria Raffaella Zocchi, Paolo Decuzzi, and Alessandro Poggi. 2020. "Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer" Cancers 12, no. 1: 104. https://doi.org/10.3390/cancers12010104

APA Style

Di Mascolo, D., Varesano, S., Benelli, R., Mollica, H., Salis, A., Zocchi, M. R., Decuzzi, P., & Poggi, A. (2020). Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer. Cancers, 12(1), 104. https://doi.org/10.3390/cancers12010104

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