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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
Nanoscale, 07/2020, Letnik: 12, Številka: 25Journal Article
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. 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.
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in: SICRIS
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