Nano-technology based carriers for nitrogen-containing bisphosphonates delivery as sensitisers of γδ T cells for anticancer immunotherapy

摘要: Nitrogen containing bisphosphonates (N-BPs) including zoledronate (ZOL) and alendronate (ALD) inhibit farnesyl diphosphate synthase, have been shown to a cytotoxic affect against cancer cells as monotherapy also sensitise tumour destruction by γδ T cells. are subset of human lymphocytes diverse range roles in the immune system recognition This property can be harnessed for use immunotherapy through vivo expansion or adoptive transfer ex activated The N-BPs with has synergistic effect vitro, animal clinical studies. limited activity due rapid clearance from circulation. By encapsulating liposomes (L) it is possible increase levels at non-osseous sites. L-ZOL L-ALD different toxicological profiles than free ZOL ALD. Both led increased spleen weight, leucocytosis, neutrophilia lymphocytopenia mice after intravenous injection. was better tolerated murine Biodistribution studies performed order understand interaction vivo. Additionally, therapy that treated both had significant reduction growth compared alone. ligand-targeted may further efficacy this combinatory immunotherapy. Liposomes targeting αvβ6 integrin receptor using peptide A20FMDV2 greater ability untargeted sensitising positive cell lines.