Preclinical evaluation of platinum-loaded hydroxyapatite nanoparticles in an embryonic zebrafish xenograft model
Robin A. Nadar, Nandini Asokan, Lorenzo Degli Esposti, Alessandra Curci, Alessandra Barbanente, Lukas Schlatt, Uwe Kärst, Michele Iafisco, Nicola Margiotta, Michael Brand, Jeroen J.J.P. van den Beucken, Martin Bornhäuser, Sander C.G. Leeuwenburgh
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.