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

doi:10.3390/cancers13215424

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.

Highlights

Ovarian cancer originating in cells on the outer surface of the ovary or in the fallopian tube epithelium is recognized as the most fatal of all gynecological tumors
We suggest that the improved killing activity of AuP@CSA-131 is determined by the enhanced uptake of ceragenin into cancer cells, which leads to autophagy over-stimulation, subsequently promoting steps that lead to the death of ovarian cancer cells
We present data supporting the utility of newly developed gold nanopeanuts as nanocarriers for the delivery of ceragenin CSA-131 into ovarian adenocarcinoma

Summary

Introduction

Ovarian cancer originating in cells on the outer surface of the ovary or in the fallopian tube epithelium is recognized as the most fatal of all gynecological tumors. Non-specific symptoms of ovarian cancer as well as a lack of universal detection methods are responsible for the high staging of the disease in 70% of patients at the beginning of treatment, which makes their prognosis for survival very poor [2]. Considering the limitations of systemic chemotherapy that result from the significant toxicity of the antineoplastic drugs associated with the administration of the high doses that are required to achieve an appropriate concentration in the target tumor, as well as the development of an accompanied drug resistance, new methods to limit cancer drug toxicity are urgently needed [4]. Cancer cell drug resistance is largely responsible for the recurrence of the disease that is observed in up to 60–80% of patients [5]. Multifunctional materials, whose unique physicochemical properties facilitate their employment for simultaneous drug delivery and imaging of therapy effectiveness, are of the greatest interest

Objectives

Methods

Results

Discussion

Conclusion