Evaluation of TFR-1 Expression in Feline Mammary Cancer and In Vitro Antitumor Efficacy Study of Doxorubicin-Loaded H-Ferritin Nanocages.

Nicolò Rensi,Laura Cavicchioli,Michela Bellini,Federico Bonsembiante,Maria Antonietta Rizzuto,Valentina Zappulli,Davide Prosperi,Silvia Ferro,Alessandro Sammarco,Filippo Torrigiani,Valentina Moccia,Rossella Zanetti,Raffaella De Maria,Alessandro Calore

doi:10.3390/cancers13061248

Abstract

Simple SummaryTransferrin receptor one (TFR-1), recognized by ferritin, is overexpressed in many tumor cells. This feature has been exploited to produce a selective overload of drugs within tumor cells by creating an engineered ferritin nanocage loaded with doxorubicin (HFn(DOX)). This bionanotechnology has been tested in human cancer, but there are no studies in veterinary oncology. This work, after evaluating the expression of TFR-1 in feline tumors, demonstrated for the first time the effectiveness in vitro of this nanocage in animals. These results confirm that engineered bionanocages also offer unprecedented opportunities for animal cancer to be applied in veterinary medicine and in comparative studies including spontaneous animal models of cancer.The transferrin receptor 1 (TFR-1) has been found overexpressed in a broad range of solid tumors in humans and is, therefore, attracting great interest in clinical oncology for innovative targeted therapies, including nanomedicine. TFR-1 is recognized by H-Ferritin (HFn) and has been exploited to allow selective binding and drug internalization, applying an HFn nanocage loaded with doxorubicin (HFn(DOX)). In veterinary medicine, the role of TFR-1 in animal cancers remains poorly explored, and no attempts to use TFR-1 as a target for drug delivery have been conducted so far. In this study, we determined the TFR-1 expression both in feline mammary carcinomas during tumor progression, as compared to healthy tissue, and, in vitro, in a feline metastatic mammary cancer cell line. The efficacy of HFn(DOX) was compared to treatment with conventional doxorubicin in feline mammary cancer cells. Our results highlighted an increased TFR-1 expression associated with tumor metastatic progression, indicating a more aggressive behavior. Furthermore, it was demonstrated that the use of HFn(DOX) resulted in less proliferation of cells and increased apoptosis when compared to the drug alone. The results of this preliminary study suggest that the use of engineered bionanocages also offers unprecedented opportunities for selective targeted chemotherapy of solid tumors in veterinary medicine.

Highlights

Feline mammary carcinomas (FMCs) are the third most common neoplasia in intact female cats, after lymphohematopoietic and cutaneous tumors [1]
Immunofluorescence The immunofluorescence assay highlighted the presence of transferrin receptor 1 (TFR-1) on FMC
We focused on the treatment of feline nanobiotechnologmyeitnasvtaettiecrminaamrymmareydciacninceer. cell line (FMCm) to test the efficacy of exploiting TFR-1 expression to obtain an intracellular drug overload [38]

Summary

Introduction

Feline mammary carcinomas (FMCs) are the third most common neoplasia in intact female cats, after lymphohematopoietic and cutaneous tumors [1]. DOX, as with most cytotoxic drugs, is known to frequently induce chemoresistance after the first set of chemotherapy cycles [14]. In this light, in the last few decades, nanotechnology has gained importance, whereby engineered nano-atomic-scale materials are applied in the biomedical field [15]. In the last few decades, nanotechnology has gained importance, whereby engineered nano-atomic-scale materials are applied in the biomedical field [15] Some nanoparticles, such as liposomes, have been designed in order to reduce cardiotoxicity effects and deliver molecules and drugs more efficiently and selectively to cancer cells [16]. Liposomal DOX has been approved and has entered the clinical practice [17]

Objectives

Methods

Results

Discussion

Conclusion