Nanoformulated zoledronic acid boosts the Vδ2T cell immunotherapeutic potential in colorectal cancer

D. Di Mascolo, S. Varesano, R. Benelli, H. Mollica, A. Salis, M.R. Zocchi, P. Decuzzi, A. Poggi

Research output: Contribution to journalArticlepeer-review

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. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
Article number104
JournalCancers
Volume12
Issue number1
DOIs
Publication statusPublished - 2020

Keywords

  • Anti-tumor immunity
  • Colorectal carcinoma
  • Polymeric nanoconstruct
  • Vδ2 T cells
  • Zoledronic acid
  • zoledronic acid
  • Article
  • cancer immunotherapy
  • cell activation
  • cell migration
  • cell proliferation
  • cell viability
  • clinical article
  • colorectal cancer
  • colorectal cancer cell line
  • controlled study
  • cytotoxicity
  • drug effect
  • drug formulation
  • electrospray mass spectrometry
  • encapsulation
  • ex vivo study
  • high performance liquid chromatography
  • human
  • human cell
  • human tissue
  • immunofluorescence
  • in vitro study
  • microfluidics
  • particle size
  • physical chemistry
  • scanning electron microscopy
  • T lymphocyte
  • tumor associated leukocyte
  • tumor spheroid

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