Anti-cancer effect of fenbendazole-incorporated PLGA nanoparticles in ovarian cancer

Abstract

Objective Fenbendazole (FZ) has potential anti-cancer effects, but its poor water solubility limits its use for cancer therapy. In this study, we investigated the anti-cancer effect of FZ with different drug delivery methods on epithelial ovarian cancer (EOC) in both in vitro and in vivo models. Methods EOC cell lines were treated with FZ and cell proliferation was assessed. The effect of FZ on tumor growth in cell line xenograft mouse model of EOC was examined according to the delivery route, including oral and intraperitoneal administration. To improve the systemic delivery of FZ by converting fat-soluble drugs to hydrophilic, we prepared FZ-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (FZ-PLGA-NPs). We investigated the preclinical efficacy of FZ-PLGA-NPs by analyzing cell proliferation, apoptosis, and in vivo models including cell lines and patient-derived xenograft (PDX) of EOC. Results FZ significantly decreased cell proliferation of both chemosensitive and chemoresistant EOC cells. However, in cell line xenograft mouse models, there was no effect of oral FZ treatment on tumor reduction. When administered intraperitoneally, FZ was not absorbed but aggregated in the intraperitoneal space. We synthesized FZ-PLGA-NPs to obtain water solubility and enhance drug absorption. FZ-PLGA-NPs significantly decreased cell proliferation in EOC cell lines. Intravenous injection of FZ-PLGA-NP in xenograft mouse models with HeyA8 and HeyA8-MDR significantly reduced tumor weight compared to the control group. FZ-PLGA-NPs showed anti-cancer effects in PDX model as well. Conclusion FZ-incorporated PLGA nanoparticles exerted significant anti-cancer effects in EOC cells and xenograft models including PDX. These results warrant further investigation in clinical trials.

Ameliorating Old Drugs with New Tricks in the Nano Realms

“…Another group attempted the delivery of fenbendazole (antihelminthic drug) to epithelial ovarian cancer via PLGA nanoparticles (FZ-PLGA-NPs). 48 The FZ-PLGA-NPs significantly decreased cell proliferation and reduced tumor weight compared with the control groups. Furthermore, as-synthesized PLGA nanoparticles have been coloaded with macrolide compound rapamycin and piperine (alkaloid) to treat multi drug resistant (MDR) breast cancer.…”

“…Tumor cell proliferation was inhibited following treatment, while there was reversion of immunosuppressive tumor microenvironment (TME). Another group attempted the delivery of fenbendazole (antihelminthic drug) to epithelial ovarian cancer via PLGA nanoparticles (FZ-PLGA-NPs) . The FZ-PLGA-NPs significantly decreased cell proliferation and reduced tumor weight compared with the control groups.…”

Fenbendazole Exhibits Differential Anticancer Effects In Vitro and In Vivo in Models of Mouse Lymphoma

“…In vitro observations do not always reflect in vivo immune responses. Previous in vivo studies have reported the anticancer effects of FBZ in SCID [25] and nude mice [22,28,29]. A study using mice with normal immunity reported no anticancer effects of FBZ [24,26].…”

Exploring treatment options in cancer: Tumor treatment strategies

“… 427 In other studies, Chi-Son Chang and colleagues reported that fenbendazole-incorporated PLGA nanoparticles exerted significant anticancer effects in epithelial ovarian cancer cells and xenograft models, including patient-derived xenografts (PDX). 428 PLGA has also been involved in preclinical studies for combination therapy. One study justifies additional preclinical safety trials and the clinical evaluation of 177Lu-PLGA(RGF)-CXCR4L as a potential combined treatment for colorectal cancer.…”