期刊
CANCERS
卷 12, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/cancers12010104
关键词
V delta 2 T cells; zoledronic acid; polymeric nanoconstruct; anti-tumor immunity; colorectal carcinoma
类别
资金
- Italian Association for Cancer Research (AIRC) [IG 21648]
- Ministero della Salute
- Ricerca Corrente 2018-2021
- Italian Association for Cancer Research [AIRC IG 17664]
- European Union [ERC 616695]
- Fondazione San Paolo project Ligurian Alliance for Nanomedicine against 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 core of spherical polymeric nanoparticles (SPNs), whose size and architecture resemble that of biological vesicles. On V delta 2 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 V delta 2 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 V delta 2 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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