DARPin_9-29-Targeted Gold Nanorods Selectively Suppress HER2-Positive Tumor Growth in Mice.

Galina M Proshkina,Anastasia V Ryabova,Victoria O Shipunova,Ivan V Zelepukin,Elena I Shramova,Alexander B Kotlyar,Sergey M Deyev,Marya V Shilova

doi:10.3390/cancers13205235

Abstract

Simple SummaryBreast cancer is one of the main causes of cancer-related death in women all around the world. The disease becomes largely incurable and lethal after metastasis to distant organs. High level of HER2, a tyrosine kinase receptor, is associated with more aggressive clinical behavior and poor prognosis for breast cancer patients. In this paper, we developed a novel nano-biomaterial for selective photothermal therapy of HER2-positive breast cancers. We demonstrate that bovine serum albumin (BSA)-coated mini gold nanorods (GNRs) chemically conjugated with a HER2-specific designed ankyrin repeat protein, DARPin_9-29, selectively accumulate in HER2-positive xenograft tumors in mice and lead to a strong reduction in the tumor size when being illuminated with near-infrared light.Near-infrared phototherapy has great therapeutic potential for cancer treatment. However, for efficient application, in vivo photothermal agents should demonstrate excellent stability in blood and targeted delivery to pathological tissue. Here, we demonstrated that stable bovine serum albumin-coated gold mini nanorods conjugated to a HER2-specific designed ankyrin repeat protein, DARPin_9-29, selectively accumulate in HER2-positive xenograft tumors in mice and lead to a strong reduction in the tumor size when being illuminated with near-infrared light. The results pave the way for the development of novel DARPin-based targeted photothermal therapy of cancer.

Highlights

Breast cancer is one of the main causes of cancer-related death in women all around the world [1,2]
Designed ankyrin repeat proteins (DARPins), which are characterized by high-affinity interaction with different epitopes of human epidermal growth factor receptor 2 (HER2), have been shown to target HER2-positive cells [12,13,14,15,16,17,18]
Conjugates of DARPins with gold nanostructures have been delivered to HER2-positive cells and the conjugate-targeted cells selectively eradicated by near-infrared (NIR) photothermal therapy [19,20]

Summary

Introduction

Breast cancer is one of the main causes of cancer-related death in women all around the world [1,2]. Trastuzumab, a HER2specific monoclonal antibody, has been used in clinical practice to treat HER2-positive breast cancer for about 20 years [7,8,9,10,11]. Designed ankyrin repeat proteins (DARPins), which are characterized by high-affinity interaction with different epitopes of HER2, have been shown to target HER2-positive cells [12,13,14,15,16,17,18]. Conjugates of DARPins with gold nanostructures have been delivered to HER2-positive cells and the conjugate-targeted cells selectively eradicated by near-infrared (NIR) photothermal therapy [19,20]. We recently demonstrated [20] that DARPin_9-29-coated gold nanorods (GNRs), DARPin-GNRs, efficiently suppress cancer cells’ growth in vitro. The reason for that was that the DARPin-coated nanorods aggregated in blood vessels after the injection

Methods

Results

Conclusion