Peanut-shaped gold nanoparticles with shells of ceragenin csa-131 display the ability to inhibit ovarian cancer growth in vitro and in a tumor xenograft model

Ewelina Piktel, Ilona Oscilowska, Łukasz Suprewicz, Joanna Depciuch, Natalia Marcińczyk, Ewa Chabielska, Przemysław Wolak, Katarzyna Głuszek, Justyna Klimek, Piotr M. Zieliński, Michał T. Marzec, Paul B. Savage, Magdalena Parlińska-Wojtan, Robert Bucki*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

Gold nanoparticles-assisted delivery of antineoplastics into cancerous cells is presented as an effective approach for overcoming the limitations of systemic chemotherapy. Although ceragenins show great potential as anti-cancer agents, in some tumors, effective inhibition of cancer cells proliferation requires application of ceragenins at doses within their hemolytic range. For the purpose of toxicity/efficiency ratio control, peanut-shaped gold nanoparticles (AuP NPs) were functionalized with a shell of ceragenin CSA-131 and the cytotoxicity of AuP@CSA-131 against ovarian cancer SKOV-3 cells and were then analyzed. In vivo efficiency of intravenously and intratumorally administered CSA-131 and AuP@CSA-131 was examined using a xenograft ovarian cancer model. Serum parameters were estimated using ELISA methods. Comparative analysis revealed that AuP@CSA-131 exerted stronger anti-cancer effects than free ceragenin, which was determined by enhanced ability to induce caspase-dependent apoptosis and autophagy processes via reactive oxygen species (ROS)-mediated pathways. In an animal study, AuP@CSA-131 was characterized by delayed clearance and prolonged blood circulation when compared with free ceragenin, as well as enhanced anti-tumor efficiency, particularly when applied intratumorally. Administration of CSA-131 and AuP@CSA-131 prevented the inflammatory response associated with cancer development. These results present the possibility of employing non-spherical gold nanoparticles as an effective nanoplatform for the delivery of antineoplastics for the treatment of ovarian malignancy.

OriginalsprogEngelsk
Artikelnummer5424
TidsskriftCancers
Vol/bind13
Udgave nummer21
Sider (fra-til)1-26
ISSN2072-6694
DOI
StatusUdgivet - 2021

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© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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