Preclinical evaluation of platinum-loaded hydroxyapatite nanoparticles in an embryonic zebrafish xenograft model. Issue 25 (19th June 2020)

• Record Type: Journal Article
• Authors: Nadar, Robin A.; Asokan, Nandini; Degli Esposti, Lorenzo; Curci, Alessandra; Barbanente, Alessandra; Schlatt, Lukas; Karst, Uwe; Iafisco, Michele; Margiotta, Nicola; Brand, Michael; van den Beucken, Jeroen J. J. P.; Bornhäuser, Martin; Leeuwenburgh, Sander C. G.
• Is Part Of: Nanoscale. Volume 12:Issue 25(2020)
• Page Start: 13582
• Page End: 13594
• Publication Date: 2020-06-19
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d0nr04064a
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : Kiteplatin-pyrophosphate (PtPP) loaded hydroxyapatite nanoparticles effectively reduce breast cancer cell in vivo, which opens up new opportunities for controlled local treatment of bone metastases. Abstract : Hydroxyapatite (HA) nanoparticles are commonly used as building blocks in the design of bone-substituting biomaterials. Recently, these nanoparticles have been considered for the treatment of metastasis disease, since their pH-dependent dissolution behavior allows for precise tuning of release kinetics of loaded cargo. Herein we show that the capacity of drug-loaded nanoparticles stabilized with citrate ions reduce cancer cell survival in an embryonic zebrafish xenograft model. In particular, in vitro studies demonstrate that PtPP-loaded HA nanoparticles exhibit anti–proliferative activity against breast cancer cells at reduced pH. In vivo studies using an embryonic zebrafish xenograft model reveal that PtPP co-delivered with human breast cancer cells strongly reduce cancer cell survival. Similarly, co-injection of breast cancer cells with citrate-functionalized and PtPP-loaded HA nanoparticles into zebrafish significantly reduces survival of cancer cells due to release of chemotherapeutically active kiteplatin species. These results demonstrate the preclinical efficacy of drug-loaded nanoparticles against human breast cancer cells in a xenogenic embryonic in vivo model.